Background Research on osteoporosis and physical activity often focuses on women. We aimed to conduct a systematic review to assess the benefits and harms of physical activity interventions for men’s bone health. Methods We used standard methods and searched for randomized controlled trials (RCTs) (duration, ≥6 months) published in all languages across multiple databases and trial registries. The last search was conducted on July 22, 2020. Results We included 11 studies (14 publications), resulting in a sample of N=723 men (range, 17–132 participants). We found low-certainty evidence that physical activity has little influence on the areal bone mineral density (aBMD) at the total hip (5 RCTs, N=324; mean difference [MD], 0.03 [95 confidence interval (CI), 0.01 to 0.05]) and little or no influence on the aBMD at the femoral neck (3 RCTs, N=186; MD, 0.00 [95% CI, −0.04 to 0.04]), lumbar spine (3 RCTs; N=213; MD, 0.05 [95% CI, −0.01 to 0.11]), and whole body (4 RCTs, N=203; MD, −0.00 [95% CI, −0.03 to 0.02]). Conclusions We found low-certainty evidence that physical activity (≥6 months) has some effect on the total hip in men, but new evidence may change this finding. This review highlights the gap in the evidence on specific intervention prescriptions that can benefit the bone geometry, structure, microarchitecture, and, ultimately, bone strength in men. Future research should engage in comprehensive reporting of harms, quality of life outcomes, advanced imaging findings, and long-term interventions.