AbstractPeople with osteoarthritis often experience pain and depression. These meta-analyses examined and compared nonpharmacological randomized controlled trials (RCTs) for pain and symptoms of depression in people living with osteoarthritis. RCTs published up until April 2022 were sourced by searching electronic databases EMBASE, PUBMED & MEDLINE, Web of Science, CINAHL and PEDro. Random-effects meta-analyses were performed to calculate pooled effect sizes (ES) and 95% confidence intervals (CI) for pain and depression. Subgroup analyses examined intervention subtypes. For pain, 29 interventions (n = 4382; 65 ± 6.9 years; 70% female), revealed a significant effect on reducing pain (ES = 0.43, 95% CI [0.25, 0.61], p < 0.001). Effect sizes were significant (p < 0.001) for movement meditation (ES = 0.52; 95% CI [0.35, 0.69]), multimodal approaches (ES = 0.37; 95% CI [0.22, 0.51]), and psychological therapy (ES = 0.21; 95% CI [0.11, 0.31]), and significant (p = 0.046) for resistance exercise (ES = 0.43, 95% CI [− 0.07, 0.94]. Aerobic exercise alone did not improve pain. For depression, 28 interventions (n = 3377; 63 ± 7.0 years; 69% female), revealed a significant effect on reducing depressive symptoms (ES = 0.29, 95% CI [0.08, 0.49], p < 0.001). Effect sizes were significant for movement meditation (ES = 0.30; 95% CI [0.06, 0.55], p = 0.008) and multimodal interventions (ES = 0.12; 95% CI [0.07, 0.18], p < 0.001). Resistance/aerobic exercise or therapy alone did not improve depressive symptoms. Mind–body approaches were more effective than aerobic/resistance exercise or therapy alone for reducing pain and depression in people with osteoarthritis.Systematic review registration: PROSPERO CRD42022338051.