The objective of this systematic review and meta-analysis was to assess the role of preoperative calcium and vitamin D supplementation in patients who underwent total thyroidectomy. The search for randomized controlled trials was performed in the OVID Medline and Embase databases. The last search was made on September 16, 2024. Three independent reviewers evaluated full-text articles from relevant reports based on eligibility criteria. The quality of the included studies was assessed by two reviewers according to the ROB 2 tool. This systematic review and meta-analysis considered 13 studies with 1504 participants. There were positive results in treatment outcomes including the mean postoperative calcium level (MD, 0.30 mg/dL: 95% CI, 0.15 to 0.44); the 48 h of postoperative hypocalcemia (OR, 0.41; 95% CI, 0.27 to 0.62); the postoperative symptomatic hypocalcemia (OR, 0.38; 95% CI, 0.24 to 0.62); the IV calcium supplementation (OR, 0.32; 95% CI, 0.18 to 0.58); and length of hospital stays (MD, -0.29; 95% CI, -0.51 to -0.07) as compared to the control group. Readmission rates showed no significant differences between the groups (OR, 0.15; 95% CI, 0.01 to 3.08). Preoperative calcium and vitamin D supplementation in patients who underwent total thyroidectomy results in reduction of postoperative symptomatic hypocalcemia. The finding is critical because it offers a feasible and effective solution that could improve patient care while potentially reducing the burden of numerous blood tests during the postoperative period. This systematic review protocol was registered with PROSPERO (registration number CRD42021278859). Level 1 Laryngoscope, 2024.