Background Instrument-assisted soft tissue mobilization (IASTM) is popular in the treatment of musculoskeletal disorders. However, the current literature has produced varying results. The purpose of this study was to collect the most recent studies to evaluate the effectiveness of IASTM on pain and function in patients with musculoskeletal disorders. Methods The researchers searched the PubMed, Embase, Web of Science, and Cochrane Library databases from inception to February 25, 2025, to identify randomized controlled trials comparing treatment groups receiving IASTM combined with other treatments to those receiving other treatments among participants with musculoskeletal disorders. The outcomes were pain intensity, pain pressure threshold and function. The Cochran Q and I-2 indices were used to estimate heterogeneity. The data were analyzed as the standardized mean difference (SMD). The Cochrane Risk of Bias tool was used to assess the risk of bias. The Grading of Recommendations Assessment, Development, and Evaluation system was used to rate the quality of evidence. Trial sequential analysis and sensitivity analyses were also performed. Results Eleven trials (involving 427 participants) were included in the quantitative analysis. Six trials had a high risk of bias; three, unclear; and two, low. There was moderate-certainty evidence indicating that IASTM was effective in reducing patient-reported pain (n = 11) (n = 427, SMD = 0.60, 95% CI: 0.41 to 0.80, p < 0.01), and there was low-certainty evidence indicating that IASTM was effective in improving patient-reported function (n = 8) (n = 333, SMD = 0.40, 95% CI: 0.03 to 0.77, p < 0.05). Only one data point was extracted for the pain pressure threshold, and a meta-analysis was not performed. Trial sequential analysis revealed that the cumulative z score crossed the monitoring boundary for superiority for patient-reported pain in patients with nonspecific chronic neck pain and cervicogenic headache at the 4-week IASTM. Conclusions IASTM can reduce patient-reported pain (with moderate certainty) and improve patient-reported function (with low certainty) in patients with musculoskeletal disorders. Future clinical studies do not need to explore the short-term effects of IASTM on patient-reported pain in patients with nonspecific chronic neck pain and cervicogenic headache.