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Context Excess calories from free sugars are implicated in the epidemics of obesity and type 2 diabetes. Honey is a free sugar but is generally regarded as healthy. Objective The effect of honey on cardiometabolic risk factors was assessed via a systematic review and meta-analysis of controlled trials using the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) approach. Data Sources MEDLINE, Embase, and the Cochrane Library databases were searched up to January 4, 2021, for controlled trials ≥1 week in duration that assessed the effect of oral honey intake on adiposity, glycemic control, lipids, blood pressure, uric acid, inflammatory markers, and markers of nonalcoholic fatty liver disease. Data Extraction Independent reviewers extracted data and assessed risk of bias. Data were pooled using the inverse variance method and expressed as mean differences (MDs) with 95%CIs. Certainty of evidence was assessed using GRADE. Data Analysis A total of 18 controlled trials (33 trial comparisons, N = 1105 participants) were included. Overall, honey reduced fasting glucose (MD = −0.20 mmol/L, 95%CI, −0.37 to −0.04 mmol/L; low certainty of evidence), total cholesterol (MD = −0.18 mmol/L, 95%CI, −0.33 to −0.04 mmol/L; low certainty), low-density lipoprotein cholesterol (MD = −0.16 mmol/L, 95%CI, −0.30 to −0.02 mmol/L; low certainty), fasting triglycerides (MD = −0.13 mmol/L, 95%CI, −0.20 to −0.07 mmol/L; low certainty), and alanine aminotransferase (MD = −9.75 U/L, 95%CI, −18.29 to −1.21 U/L; low certainty) and increased high-density lipoprotein cholesterol (MD = 0.07 mmol/L, 95%CI, 0.04–0.10 mmol/L; high certainty). There were significant subgroup differences by floral source and by honey processing, with robinia honey, clover honey, and raw honey showing beneficial effects on fasting glucose and total cholesterol. Conclusion Honey, especially robinia, clover, and unprocessed raw honey, may improve glycemic control and lipid levels when consumed within a healthy dietary pattern. More studies focusing on the floral source and the processing of honey are required to increase certainty of the evidence. Systematic Review Registration PROSPERO registration number CRD42015023580.