Background: Production of reactive oxygen species (ROS) by polymorpho nuclear neutrophils occurs in chronic periodontitis. These ROS are mainly involved in bacterial destruction. However, extracellular release of same results in destruction of surrounding tissue. Spirulina, a potent antioxidant when administered sub gingivally in pockets can offer improved results in chronic periodontitis patients. This study was conducted to evaluate the effect of Spirulina when delivered sub gingivally in patients with chronic periodontitis. Methods: Sixty chronic periodontitis patients were divided into 2 groups. Group I (n = 30) were treated with Scaling and Root planning (SRP) followed by placement of placebo (SRP-P) and in Group II (n = 30) Spirulina microspheres were placed sub gingivally (SRP-S) following SRP. Clinical parameters like bleeding on probing (BOP), clinical attachment level (CAL), gingival index (GI) and probing pocket depth (PPD) were evaluated. Levels of salivary and serum Malondialdehyde (MDA) were estimated using ultra violet spectrophotometer. Results: At baseline, in both groups there was no statistically significant difference in clinical and biochemical parameters. Intra group comparisons of parameters from baseline to 90 days were statistically significant in both groups. After 90 days difference in clinical parameters and salivary MDA levels were statistically significant in SRP-S compared to SRP-P group. Though serum MDA levels were reduced in both groups, they were not significant statistically. Conclusions: Our study concluded that, local drug delivery of Spirulina adjunctive to SRP has potent antioxidant effect in treatment of chronic periodontitis.