Solvent exchange-induced in situ forming gel (ISG) has emerged as a versatile drug delivery system, particularly for periodontal pocket applications. In this study, we developed lincomycin HCl-loaded ISGs using a 40% borneol-based matrix and N-methyl pyrrolidone (NMP) as a solvent. The physicochemical properties and antimicrobial activities of the ISGs were evaluated. The prepared ISGs exhibited low viscosity and reduced surface tension, allowing for easy injection and spreadability. Gel formation increased the contact angle on agarose gel, while higher lincomycin HCl content decreased water tolerance and facilitated phase separation. The drug-loading influenced solvent exchange and matrix formation, resulting in thinner and inhomogeneous borneol matrices with slower gel formation and lower gel hardness. The lincomycin HCl-loaded borneol-based ISGs demonstrated sustained drug release above the minimum inhibitory concentration (MIC) for 8 days, following Fickian diffusion and fitting well with Higuchi’s equation. These formulations exhibited dose-dependent inhibition ofStaphylococcus aureusATCC 25923,Escherichia coliATCC 8739, andProphyromonas gingivalisATCC 33277, and the release of NMP effectively inhibitedCandida albicansATCC 10231. Overall, the 7.5% lincomycin HCl-loaded 40% borneol-based ISGs hold promise as localized drug delivery systems for periodontitis treatment.