BackgroundLimited evidence is available on the dose-dependent effects of calorie restriction in patients with type 2 diabetes. ObjectivesWe aimed to gather available evidence on the effect of calorie restriction on the management of type 2 diabetes. MethodsWe systematically searched PubMed, Scopus, CENTRAL, Web of Science, and gray literature until November 2022 for randomized trials >12 wk looking at the effect of a prespecified calorie-restricted diet on remission of type 2 diabetes. We performed random-effects meta-analyses to estimate the absolute effect (risk difference) at 6-mo (6 ± 3 mo) and 12-mo (12 ± 3 mo) follow-ups. Then, we performed dose–response meta-analyses to estimate the mean difference (MD) for the effects of calorie restriction on cardiometabolic outcomes. We used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to judge the certainty of evidence. ResultsTwenty-eight randomized trials with 6281 participants were included. Using a remission definition of an HbA1c level of <6.5% without antidiabetic medication use, calorie-restricted diets increased remission by 38 more per 100 patients (95% CI: 9 more, 67 more; n = 5 trials; GRADE = moderate) at 6 mo and by 13 more per 100 patients (95% CI: 10 more, 18 more; n = 4; GRADE = moderate) at 12 mo in comparison to usual diet or usual care. Using a definition of HbA1c of <6.5% after at least 2-mo cessation of antidiabetic medications, remission increased by 34 more per 100 patients (95% CI: 15 more, 53 more; n = 1; GRADE = very low) at 6 mo and by 16 more per 100 patients (95% CI: 4 more, 49 more; n = 2; GRADE = low) at 12 mo. At 6 mo, each 500-kcal/d decrease in energy intake resulted in clinically meaningful reductions in body weight (MD: −6.33 kg; 95% CI: −7.76, −4.90; n = 22; GRADE = high) and HbA1c (MD: −0.82%; 95% CI: −1.05, −0.59; n = 18; GRADE = high), which attenuated remarkably at 12 mo. ConclusionsCalorie-restricted diets may be effective intervention for type 2 diabetes remission, especially when coupled with an intensive lifestyle modification program.This systematic review was registered in PROSPERO as CRD42022300875 (https://www.crd.york.ac.uk/prospero/display_record.php?RecordID = 300875).Am J Clin Nutr 2023;xxx:xx–xx.