SummaryIntracranial pressure is one of the determinants of sympathetic activities, and sleep bruxism is associated with increased sympathetic activities. This study aimed to investigate effects of the low Fowler's sleep position and methazolamide treatment on the occurrence of rhythmic masticatory muscle activities/sleep bruxism episodes in patients with sleep bruxism in a randomized controlled trial. Polysomnographic recordings were performed on the patients with sleep bruxism sleeping in the low Fowler's (15°–30°) or supine position (n = 11), and with methazolamide or placebo treatment (100 mg, 3–4 hr before bedtime, P.O., n = 9), and changes in sleep variables and heart rate variance during sleep in the low Fowler's position or with methazolamide treatment were determined. Sleep bruxism index, number of masseter muscle electromyographic bursts per hour of sleep, ratio of rhythmic masticatory muscle activities/sleep bruxism duration to the total sleep duration, index of total limb movements, index of limb movements with rhythmic masticatory muscle activities, and number of sleep bruxism clusters per hour of sleep in the low Fowler's position and after methazolamide intake were significantly smaller (p < 0.05–0.001) than those in the supine position and after placebo intake, respectively. The low‐frequency heart rate variance powers during non‐rapid eye movement sleep stage 2 (N2) in the low Fowler's position and with methazolamide treatment were significantly lower (p < 0.05) than those during sleep in the supine position and with placebo treatment, respectively. In conclusion, sleep in the low Fowler's position and methazolamide treatment were associated with significant decreases in the occurrence of rhythmic masticatory muscle activities/sleep bruxism episodes, which might be due to a reduction in intracranial pressure and sympathetic activities mainly during non‐rapid eye movement sleep stage 2.