For menstrual cramps, anti-inflammatory painkillers like ibuprofen and naproxen are the most effective over-the-counter options, outperforming both placebo and acetaminophen by a significant margin. For muscle cramps and stomach cramps, the best medicine depends on the underlying cause, but effective options exist for each type.
Why Anti-Inflammatories Work Best for Period Cramps
During your period, the lining of your uterus releases chemicals that trigger inflammation and cause the uterine muscle to contract. These contractions are what you feel as cramps. Anti-inflammatory painkillers (NSAIDs) work by blocking your body from producing those chemicals in the first place, which is why they’re more effective than plain painkillers like acetaminophen, which only block pain signals without addressing the inflammation driving the contractions.
A large Cochrane review of 35 randomized trials found that NSAIDs provided moderate or excellent pain relief for 45% to 53% of women, compared to just 18% of women taking a placebo. When compared head-to-head with acetaminophen (Tylenol), NSAIDs were nearly twice as effective at relieving pain. Seattle Children’s Hospital puts it bluntly: acetaminophen products “are not helpful for menstrual cramps.”
Ibuprofen vs. Naproxen for Menstrual Pain
The two most accessible NSAIDs are ibuprofen (Advil, Motrin) and naproxen (Aleve). Research comparing individual NSAIDs against each other has found little evidence that any single one is superior for pain relief or safety. In practice, ibuprofen is the usual starting point because it’s cheap, widely available, and works quickly. If ibuprofen doesn’t provide enough relief, naproxen is a solid alternative. It lasts longer per dose, so you take it less frequently throughout the day.
For naproxen, the NHS recommends starting with 500 mg, then taking 250 mg every 6 to 8 hours as needed, with a maximum of 1,250 mg per day after the first day. For ibuprofen, standard OTC dosing is 200 to 400 mg every 4 to 6 hours.
Timing Matters More Than You Think
The single best thing you can do to get more out of your cramp medication is to start taking it early. Because NSAIDs work by preventing the buildup of inflammatory chemicals, they’re most effective when you take them right before or at the very start of your period, before cramps intensify. Waiting until the pain is already severe means those chemicals have already been released and are harder to counteract. If your cycle is predictable, start dosing at the first sign of bleeding or even just before.
Who Should Avoid NSAIDs
NSAIDs are safe for most people when used for a few days each cycle, but they aren’t right for everyone. You should avoid them or talk to a provider first if you have kidney problems, a history of stomach ulcers, heart disease, or high blood pressure. People who are dehydrated or who take blood pressure medications (particularly ACE inhibitors or diuretics) face a higher risk of kidney injury from NSAIDs. The combination of an ACE inhibitor, a diuretic, and an NSAID is sometimes called the “triple whammy” for kidney risk. If NSAIDs are off the table for you, a provider can discuss prescription alternatives, including antispasmodic medications that relax the uterine muscle directly.
Side effects at normal doses are relatively mild. The Cochrane review found that about 11% to 14% of NSAID users experienced side effects (mostly stomach upset or headaches), compared to 10% of those taking a placebo.
Best Medicine for Muscle Cramps
Leg cramps and other skeletal muscle cramps are a different problem with different solutions. NSAIDs won’t do much here because muscle cramps aren’t driven by the same inflammatory process as period cramps. They’re caused by involuntary muscle contractions, often related to dehydration, electrolyte imbalances, or nerve signaling issues.
Magnesium is the most widely discussed supplement for muscle cramps, but the evidence is nuanced. Short courses of magnesium (under 60 days) have not been shown to help. However, a randomized controlled trial of 184 people found that taking 226 mg of magnesium oxide daily for at least 60 days cut cramp frequency from about 5.4 episodes per week down to 1.9, compared to a drop from 6.4 to only 3.7 in the placebo group. Cramp duration also dropped significantly. So magnesium may help, but only if you commit to taking it consistently for two months or more.
Prescription muscle relaxants exist but are not first-line treatments. Providers typically try other approaches first and only prescribe relaxants when those fail. These medications, such as cyclobenzaprine or methocarbamol, are mainly used for musculoskeletal pain and back spasms rather than simple nocturnal leg cramps.
Best Medicine for Stomach and GI Cramps
Abdominal cramps caused by conditions like irritable bowel syndrome (IBS), colon spasms, or functional digestive issues involve your smooth muscles, the involuntary muscles that line your gut. These respond to a class of prescription medications called antispasmodics, which block the nerve signals telling those muscles to contract. The most commonly prescribed ones in the U.S. include dicyclomine and hyoscyamine.
Antispasmodics are also sometimes used for bladder spasms, gallbladder pain, and even menstrual cramps when NSAIDs aren’t an option. Because they slow down gut movement, they can cause constipation, so they’re worth discussing with a provider if that’s already a problem for you. Unlike NSAIDs, antispasmodics are not available over the counter. For occasional mild stomach cramps not tied to a diagnosed condition, simethicone (for gas-related cramping) or peppermint oil capsules are common OTC options, though their evidence base is more limited.