Murine double minute 2 (MDM2) plays an important role in the carcinogenesis of many cancers including osteosarcoma. We performed a systemic review and meta-analysis to assess the effects of MDM2 polymorphisms on osteosarcoma risk and survival of patients with osteosarcoma. PubMed, Web of Science, and Wanfang databases were searched for eligible studies on the associations of MDM2 polymorphisms with osteosarcoma risk and survival of patients with osteosarcoma. Pooled odds ratio (OR) or hazard ratio (HR) with 95 % confidence intervals (95 % CIs) was used to assess the effects of MDM2 polymorphisms on osteosarcoma risk and survival of patients with osteosarcoma. Overall, MDM2 rs2279744 polymorphism was associated with a risk of osteosarcoma (allele model, OR = 1.60, 95 % CI 1.23-2.07, P < 0.001; codominant model, OR = 2.47, 95 % CI 1.46-4.19, P = 0.001; recessive model, OR = 2.13, 95 % CI 1.32-3.46, P = 0.002; dominant model, OR = 1.61, 95 % CI 1.12-2.33, P = 0.01). MDM2 rs1690916 polymorphism was also associated with a risk of osteosarcoma (OR = 0.60, 95 % CI 0.46-0.77, P < 0.001). However, MDM2 rs2279744 polymorphism was not associated with the overall survival of patients with osteosarcoma (codominant model, HR = 1.01, 95 % CI 0.53-1.91, P = 0.98; recessive model, HR = 1.07, 95 % CI 0.54-2.11, P = 0.85; dominant model, HR = 1.04, 95 % CI 0.65-1.66, P = 0.87). The meta-analysis suggests that MDM2 polymorphisms have some effects on the risk of osteosarcoma but have no effect on the survival of patients with osteosarcoma. Future studies are needed to further assess the effects of MDM2 polymorphisms on the risk and survival of osteosarcoma.