Background <p>Mental fatigue (MF) is a psychobiological state that impairs physical and cognitive performance, particularly in endurance and resistance tasks. Transcranial direct current stimulation (tDCS) has emerged as a promising noninvasive neuromodulation technique to mitigate MF and increase exercise capacity. However, evidence remains inconsistent due to methodological heterogeneity in stimulation parameters, fatigue induction protocols, and outcome assessments. This research aims to systematically review randomized controlled trials (RCTs) investigating the effects of active versus sham tDCS on reducing MF and improving physical performance, such as time to exhaustion and muscular endurance, in healthy, physically active adults, including athletes.</p> Methods <p>This protocol follows the PRISMA-P guidelines and is registered with PROSPERO (CRD4202541050229). Eligible studies will include RCTs (parallel or crossover) comparing active tDCS (any validated protocol) with sham stimulation in adults ≥ 18 years of age without neurological, psychiatric, or cardiovascular conditions. Searches will be conducted in PubMed, Embase, Scopus, Web of Science, SPORTDiscus, PsycINFO, and ClinicalTrials.gov. Primary outcomes are time to exhaustion and number of repetitions to failure; secondary outcomes include MF scores. Two independent reviewers will select studies, extract data, and assess risk of bias using Cochrane RoB 2.0. Metaanalyses will be performed where possible, with subgroup, sensitivity, and metaregression analyses as appropriate.</p> Discussion <p>This review will synthesize the available evidence on the efficacy of tDCS on MF and physical performance in healthy adults. The results aim to inform the design of future research and support the standardization of tDCS protocols in sport and exercise science.</p> Systematic review registration <p>PROSPERO&#xa0;CRD420251050229</p>