Research objective: The aim of this study was to examine whether inositol hexaphophate in addition to nonsurgical mechanical periodontal therapy has a significant effect in therapy of third and fourth stage periodontitis compared to chlorhexidine. Additionally the effect of administering inositol hexaphosphate on systemic inflammation parameters was examined. Materials and methods: The study was conducted as randomized clinical trial. 13 participants were included, all with stage three and four periodontitis. Participants were divided into three groups. First group (N=4) used inositol hexaphosphate after mechanical nonsurgical periodontal therapy. The second group (N=4) used chlorhexidine after nonsurgical mechanical periodontal therapy. The third group (N=5) used inositol hexaphosphate before the mechanical nonsurgical periodontal therapy. Parameters measured in this study were probing depth (PD), clinical attachment level (CAL), plaque index (PI), bleeding on probing (BOP), blood glucose level (GUK), sedimentation (SE), fibrinogen, and C reactive protein (CRP), pH of urine and relative volume mass of urine. Results: Use of chlorhexidine after nonsurgical mechanical periodontal therapy showed a statistically significant reduction in plaque index (P=0,03) and probing depth (P=0,02), while use of inositol hexsaphosphate showed statistically significant reduce in bleeding on probing (P=0,01). In comparison results of the first two groups showed no statistically significant difference. The results of the third goup of participants showed no statistically effect on systemic inflammation parameters, while it showed statistically significant effect on plaque index(P=0,04), bleeding on probing (P=0,03) and probing depth (P=0,01). Conclusion: ReThe study shows that inositol hexaphosphate does not have a greater significance in therapy of third and fourth stage periodontitis in addition to nonsurgical mechanical periodontal therapy compared to use of chlorhexidine. Also, inositol hexaphosphate does not have a significant effect on systemic parameters of inflammation, administered before the nonsurgical mechanical periodontal therapy. More research is needed in order to confirm this conclusion.