Athletes of various sports are required to utilize mouthguards during practice and competitions for protection against orofacial and dental injuries, regardless of the effects on performance. Recent advances in neuromuscular dentistry have led to the development of a mouthguard touted also to enhance the performance through jaw realignment. The purpose of this study was to compare the effects of a neuromuscular dentistry-based mouthguard to a standard, custom-fitted mouthguard (CFM) on muscular endurance, anaerobic power and anaerobic capacity in competitive athletes. Professional and Division I college athletes (n = 22, Mweight = 86.2 ± 3.1 kg) participated in this double-blind, crossover study. Subjects were randomly assigned to order of use of either the experimental (Pure Power Mouthguard (PPM)) or the traditional CFM. Subjects completed two separate sessions in which they completed three performance tests, which included vertical jump (VJ), bench press (BP) and a 30 s Wingate anaerobic test (WAnT)+eight 10 s intervals, while wearing the assigned mouthguard. Significantly better performance was found for PPM compared with CFM for VJ (67.6+9.4 cm vs. 65.3+8.6 cm; P = 0.003), 30 s WAnT peak power (11.6 ± 1.7 W kg− 1vs. 11.1 ± 1.5 W kg− 1, P = 0.038), average peak power for WAnT+intervals (10.6 ± 1.4 W kg− 1vs. 10.1 ± 1.2 W kg− 1, P = 0.025) and average mean power for WAnT+intervals (9.0 ± 1.1 W kg− 1vs. 8.7 ± 1.0 W kg− 1, P = 0.034). There were no significant differences for either BP or 30 s WAnT mean power (P>0.48). Compared with a CFM, a neuromuscular dentistry-based mouthguard appears to enhance peak power output, performance and repeated maximal efforts. When required to wear a mouthguard, athletes may benefit from wearing a neuromuscular dentistry-designed mouthguard compared with a CFM.