Background: Reduction of ectopic fat accumulation plays an important role in the prevention of insulin resistance in people with overweight or obesity. This systematic review and meta-analysis summarizes the current evidence for the use of noninvasive weight loss interventions (exercise or diet) on ectopic fat. Methods: A systematic literature search was performed according to the PRISMA statement. Clinical trials in PubMed, PEDro, and the Cochrane database were searched. Results: All 33 included studies described the effect of lifestyle interventions on ectopic fat storage in internal organs (liver, heart, and pancreas) and intramyocellular lipids (IMCL), hereby including 1146, 157, 87, and 336 participants. Overall, a significant decrease of ectopic fat was found in liver (-0.53 Hedges' g, P < .001), heart (-0.72 Hedges' g, P < .001) and pancreas (-0.55 Hedges' g, P = .098) respectively. A trend toward decrease in IMCL was also observed. Meta-regression indicated a dose-response relationship between BMI reduction and decreased hepatic adiposity. Exercise alone decreased ectopic fat but the effect was greater when combined with diet. Conclusion: Lifestyle interventions can reduce ectopic fat accumulation in the internal organs of overweight and obese adults. The results on IMCL should be interpreted with care, keeping the 'athlete's paradox' in mind.