Invasive techniques like percutaneous electrolysis have recently surged in popularity for treating musculoskeletal disorders. However, emerging techniques have sparked debates on the current needed to achieve optimal results. The aim of this review was to compare the effects of electrolysis and microelectrolysis on pain intensity in individuals with musculoskeletal pain. This quantitative systematic review has an observational, retrospective, and secondary design. The search included databases such as PubMed, Scopus, Web of Science, EMBSCOhost, Embase, Cochrane Library, PEDro, and Google Scholar (updated on July 1, 2024). Independent reviewers selected eligible studies and assessed their quality using the Cochrane risk of bias 2 tool. The primary outcome was pain intensity, while secondary outcomes included pain pressure threshold and disability. The meta-analysis calculated pooled effects using mean differences or standardized mean differences for these outcomes. Twenty-eight studies were included with an overall low risk of bias (21.4%). Randomization and outcome measurement (21.4%), intervention deviations (28.6%), and outcome measurement (53.6%) were all sources of bias. Statistically-significant reductions in pain intensity and disability (p < 0.01) were observed post-treatment for both microelectrolysis (pain: SMD = -0.92; 95% CI: -1.3, -0.5 and disability: SMD = -0.92; 95% CI: -1.3, -0.5) and electrolysis (pain: SMD = -0.3; 95% CI: -0.6, -0.01 and disability: SMD = -1.8; 95% CI: -3.1, -0.6). For the pain pressure threshold, neither modality outperformed the controls. This review highlights the effectiveness of electrolysis modalities in the treatment of musculoskeletal pain and disability, especially microelectrolysis, which shows a larger effect in terms of pain reduction. Further research is needed to understand their analgesic mechanisms, and US-guided decisions should be based on comprehensive risk-benefit assessments.