Worldwide prevalence of adult overweight and obesity is a growing public health issue. Adults with overweight/obesity often have chronic musculoskeletal pain. Using a mixed-methods review, we aimed to quantify the effectiveness and explore the appropriateness of weight-loss interventions for this population. Electronic databases were searched for studies published between 01/01/90-01/0716. The review included 14 randomised controlled trials that reported weight and pain outcomes and three qualitative studies that explored perceptions of adults with co-existing overweight/obesity and CMP. The random-effects pooled mean weight-loss was 4.9kg (95%CI:2.9,6.8) greater for intervention vs control. The pooled mean reduction in pain was 7.3/100units (95%CI:4.1,10.5) greater for intervention vs control. Study heterogeneity was substantial for weight loss (I2=95%, tau=±3.5kg) and pain change (I2=67%, tau=±4.1%). Meta-regression slopes for the predictors of study quality, mean age and baseline mean weight on mean study weight reduction were shallow and not statistically significant (P>0.05). The meta-regression slope between mean pain reduction and mean weight lost was shallow, and not statistically significant, -0.09kg per unit pain score change (95%CI:-0.21,0.40,p=0.54). Meta-synthesis of qualitative findings resulted in two synthesized findings; the importance of healthcare professionals understanding the effects of pain on ability to control weight, and developing management/education programmes that address comorbidity.