Manual recordkeeping for Schedule II–V controlled substances in Nigerian research laboratories creates persistent risks: data manipulation, weak audit trails, delayed discrepancy detection, and unauthorized access. This study analyzed regulatory requirements under the NAFDAC Act and NDLEA Act, reviewed recent NAFDAC enforcement actions (2023–2025), and designed an automated system integrating RFID tracking, biometric authentication, and tamper-proof digital audit trails. A discrete-event simulation model (built in Excel and Python) compared manual and automated workflows using 12 months of historical transaction data from a Nigerian biomedical laboratory. The automated system eliminated inventory discrepancies (reducing the average discrepancy from 4.8% to 0.1%), cut compliance reporting time from 4.2 hours to 1.1 hours per week (73% reduction), and shortened discrepancy detection lag from 15 days to under 2 minutes. The system also satisfied ALCOA+ data integrity principles and the physical security requirements of NAFDAC’s *Drugs and Related Products (Registration) Regulations, 2021*. We conclude that automation significantly improves security, traceability, and regulatory compliance for Nigerian research institutions. Future work should include live deployment and cost-benefit analysis.