Aim <p>This randomized controlled trial aimed to evaluate the clinical efficacy of 4% Shyama Tulsi (Ocimum Sanctum Linn) extract impregnated with Calcium Sulphate Hemihydrate as a localized alternative to systemic antibiotics following simple tooth extraction.</p> Materials and Methods <p>A total of 160 patients (<i>n</i> = 80 per group) aged 18–60 years requiring tooth extraction via a closed technique were enrolled. Patients were randomly assigned to Group A (control) or Group B (study). The control group received antibiotics and analgesics twice daily, while the study group received 4% Shyama Tulsi extract with Calcium Sulphate Hemihydrate in the socket and a single analgesic postoperatively. The primary objectives were pain and infection, while the secondary objectives included dry socket and any other complications. Patients were assessed clinically on Days 1, 3, and 7, with daily telephone follow-ups.</p> Results <p>A total of 242 extractions were performed in 160 patients. Among the 112 extractions in the study group, only 6 patients (6.3%) reported pain on the first day, with 7 (7.6%) requiring one painkiller at night. By day 2, 7 patients reported pain, with 6 consuming one tablet in the morning. No patients developed an infection or dry socket. Age and gender distribution between groups were statistically nonsignificant.</p> Conclusion <p>The combination of 4% Shyama Tulsi extract with Calcium Sulphate Hemihydrate shows promise as an effective alternative to systemic antibiotics and painkillers in simple tooth extractions.</p>