Aim: The aim of this study was to determine the presence, concentrations, dietary intake, and risk of residues of neonicotinoids (NEO) and insect growth regulators (IGR) in commercially available honey in South Africa. Methods: Sample preparation for honey was based on the “dilute and shoot” principle, followed by analysis using an internally validated ultra-high-performance liquid chromatographic coupled to tandem mass spectrometric method. Estimated daily intake and acute and chronic hazard quotients were determined to measure human exposure and health risk to NEO and IGR as well as the risk posed to honeybee. Results: NEO and IGR were detected in 50% and 21% of the 115 honey samples, respectively. The average concentration ranged 0.062-6.50 µgkg-1 and 0.479-1.644 µgkg-1 for NEO and IGR, respectively. While acetamiprid was the most detected (24.35%) NEO, imidacloprid presented the highest concentration (16.945 µg kg-1) in a sample. IGR co-occurred at variable concentrations with NEO in honey samples. The estimated daily intakes (EDI) of NEO and IGR ranged from 9.35 × 10-7 to 4.93 × 10-6 mg kg-1 bwd-1. The chronic hazard quotient (HQc) and acute hazard quotient (HQa) for NEO and IGR were considerably < 1, indicating negligible risk to human health and honeybee population. Conclusion: A UHPLC-MS/MS method was validated for the simultaneous determination of neonicotinoids and insect growth regulators in honey. Overall, the result of the present study confirms the widespread occurrence of NEO and IGR in honey consumed in South Africa. The EDIs, HQc, and HQa indicate that exposure to all target NEO and IGR via honey consumption constitutes negligible human health risk; however, the consequences of multiple routes of exposure to NEO and IGR cannot be overemphasized.