Aim: This research was conducted to analyze and compare the regenerative ability of 1% alendronate (ALN) and 1% metformin (MF) in chronic periodontitis patients with infrabony defects. Materials and methods: This study had a split-mouth design in which 26 sites with infrabony defects in chronic periodontitis patients were enrolled; 13 were aggregated to the group I (1% ALN gel) and 13 to group II (1% MF gel). A follow-up period of 3 and 6 months was observed postoperatively for the clinical parameters, and a follow-up of 6 months was observed radiologically, after which the data collected was analyzed. Results: Both groups demonstrated statistically significant probing pocket depth reduction, defect depth reduction (DDR), and relative attachment level gain at an interval of 6 months. However, no statistically significant distinction was observed among the groups in both clinical and radiographic measures, as well as crestal bone loss. Conclusion: Within the constraints of our study, no difference in the efficacy of 1% MF and 1% ALN was observed in periodontal therapy of chronic periodontitis patients with infrabony defects. Clinical significance: About 1% ALN and 1% MF have been shown to regenerate periodontal structures and, hence, can be used in the treatment of periodontitis, owing to their antiresorptive and bone-stimulating ability.