To prepare and characterize linezolid-based hydrogel and evaluate its efficacy as local drug delivery in stage II grade A periodontitis. Linezolid-based hydrogel was prepared. Hemolysis assay was done at various concentrations (2%, 4%, 6%, 8%, 10%) and a biocompatibility test was performed by MTT Assay. Forty patients with stage II grade A periodontitis were involved in this clinical trial. Participants were split into two groups. Group A (control) received only scaling and root planing (SRP) and Group B (test) received linezolid gel along with SRP. Clinical data were recorded, including plaque index (PI), gingival index (GI), probing pocket depth (PPD), clinical attachment level (CAL) at baseline and after 3 months. In vitro analysis revealed that at 2% concentration, the hemolysis ratio was less than 1% and 98% cell viability was observed after 94 hours in biocompatibility assay. 2% Linezolid-based hydrogel was subjected to in vivo analysis. Upon intra-group comparison, all the clinical parameters (PI, GI, PPD, CAL) showed statistically significant differences (p<0.05) from baseline to 3 months. Also on the inter-group comparison, a significant difference was evident in all parameters in favor of Group B (p<0.05). For patients with stage II grade A periodontitis, locally administered linezolid gel seems to be effective as an adjunct to SRP.