Background: Preventing contrast-induced acute kidney injury (CI-AKI) is critical because of its association with poor clinical outcomes, including extended hospital stays and increased mortality. The effects of probucol on preventing CI-AKI have been controversial. Therefore, this systematic review and meta-analysis evaluated the influence of probucol combined with hydration on the CI-AKI risk in patients with coronary heart disease undergoing coronary angiography (CAG) or percutaneous coronary intervention (PCI). Methods: We retrieved data from the following databases from their inception to May 29, 2022: PubMed, Embase, Web of Science, Cochrane Library, China National Knowledge Infrastructure, Chinese Biomedical Literature Database (Sinomed), Wanfang Database, and Chinese Scientific Journal Database. The methodological quality of the trials was assessed following the Cochrane Handbook guidelines, and Review Manager 5.3 and Stata 14.0 software were used for the data analysis. Results: We included 14 trials comprising 3306 patients in the analysis. All included trials reported the CI-AKI incidence rate (the primary outcome). Probucol with hydration significantly reduced the CI-AKI incidence compared to hydration alone (odds ratio [OR]: 0.33, 95% confidence interval [CI]: 0.25–0.44, P < .001). Subgroup analyses were performed based on the contrast medium type (iso-osmolality vs low-osmolality contrast medium [LOCM]) and volume (less than or more than 200 mL); the effects of probucol with hydration versus hydration-only on CI-AKI were comparable within each subgroup. Additionally, the serum creatinine (Scr) concentration 24 hours, 48 hours, and 72 hours and the estimated glomerular filtration rate (eGFR) 72 hours after contrast exposure were better in the probucol with hydration group than the hydration-only group. Finally, major clinical adverse events and adverse drug reactions were comparable between the probucol with hydration and hydration-only groups. Conclusion: Probucol with hydration decreases the CI-AKI incidence compared to hydration only in patients with coronary heart disease undergoing CAG or PCI. However, more high-quality, large-sample, multicenter randomized trials are needed to confirm this conclusion.