BACKGROUND: It is widely acknowledged that eccentric muscle contractions may cause skeletal muscle damage. However, there is little knowledge about the impact of eccentric contractions on non-muscular structures. Animal and human studies revealed that eccentric contractions can also induce immediate and short-term nerve dysfunction. The purpose of this review is to examine whether eccentric muscle contractions induce immediate and short-term effects on structural, morphological, mechanical, functional and physiological properties of peripheral nerves, from both animal and human studies. METHODS AND ANALYSIS: A systematic review of randomised (RCTs) and non-randomised controlled trials will be conducted. Four electronic databases (i.e., Medline/Pubmed, Science Direct, PEDro and Cochrane) will be searched using predefined search terms to identify relevant studies. Eligible studies have to comprise any type of eccentric contraction of upper or lower limb muscles. Primary outcomes will include measures related to structure, morphology, mechanical, functional and physiological properties of peripheral nerves. Two independent reviewers will assess eligibility, evaluate risk of bias, and extract relevant data. In human studies, the risk of bias will be assessed by the Cochrane Collaboration risk of bias tool (RoB 2.0 tool) for RCTs and by risk of bias in non-randomised studies of interventions (ROBINS-I) for non-randomised controlled trials; while for animal studies, the risk of bias will be assessed using the SYRCLE's RoB tool. A narrative synthesis will be conducted for all included studies. Also, if appropriate, a meta-analysis will be performed, where the effect size of each outcome will be determined by the standardized mean difference as well as the 95% confidence intervals. I2 statistics will be used to assess heterogeneity. ETHICS AND DISSEMINATION: For this study, no ethical approval is required. Findings will be disseminated widely through peer-reviewed publication and conference presentations. SYSTEMATIC REVIEW REGISTRATION: The protocol has been registered at the International Prospective Register of Systematic Reviews (PROSPERO). Registration number: CRD42021285767.