This study evaluates the catalytic efficiency of free laccase and laccase entrapped in mesoporous silica microparticles (LSM) for the degradation of oxytetracycline (OTC) in aqueous media. The LSM system demonstrated a degradation efficiency of up to 82% within 24 hours, outperforming the free enzyme in terms of pH tolerance and operational stability. Temperature-dependent experiments revealed that degradation at elevated temperatures was primarily due to OTC thermal instability rather than enzymatic activity. Furthermore, LSM retained approximately 90% of its degradation capacity after seven reuse cycles, indicating strong potential for repeated application. These findings underscore the applicability of LSM as a robust biocatalyst for antibiotic remediation in water treatment systems.