Pharmaceutical SMEs in Peru face significant logistical challenges, particularly in their On-Time In-Full (OTIF) performance. Prior research suggests that Lean Six Sigma, combined with Kotter’s Change Management model, can effectively reduce operational inefficiencies, yet most studies focus on larger enterprises. This study addressed urgent issues like procurement delays and packaging errors by applying the DMAIC framework and Kotter’s model to ensure successful implementation of new practices. The objective was to enhance OTIF and streamline operations. Results showed a 40% reduction in dispatch times and a 15.66% improvement in OTIF, rising from 81.5% to 94.26%, with procurement efficiency increasing by 23.29%. This research contributed to the literature by integrating Lean Six Sigma and Kotter’s model in SMEs, improving competitiveness and operational performance in the pharmaceutical sector. Future research should explore broader applications of these methodologies in SME logistics across various industries.