Background: Periodontal diseases are inflammatory reactions that affect the supporting tissues of the teeth, which consist of Gingiva, periodontal ligament, root cementum and alveolar bone. The third generation of cephalosporins - cefixime (CEF), which is an antibiotic with wide spectrum of effect on Gram-positive and Gramnegative bacteria, was used in cases of oral infections. Objective: The aim of the study to evaluate the efficacy of non-surgical therapy and combination of amoxicillin and metronidazole compared with cefixime. Methods: The clinical study was conducted at the Department of Periodontology, Clinic for Dentistry of the Khulna Medical College. In order to assess the condition of periodontium, we used the level of gingival inflammation which is expressed through gingival index (GI) according to Loe and Silness, bleeding on probe (BOP), according to M?hlemann and Son, probing depth (PD) and clinical attachment level (CAL). Results: In control group, mean gingival index, bleeding on probing and probing pocket depth were statistically significantly (p<0.05) when compare between day 0 vs day 7. In AMO-MET group, mean gingival index, bleeding on probing and probing pocket depth were statistically significantly (p<0.05) when compare between day 0 vs day 7. In cefixime mean gingival index, bleeding on probing and probing pocket depth were statistically significantly (p<0.05) when compare between day 0 vs day 7. After seventh day, mean bleeding on probing and probing pocket depth were statistically significantly when compared between control vs AMO-MET and control vs cefixime group. Conclusion: Mean bleeding on probing and probing pocket depth was statistically significantly when compared between control vs AMO-MET and control vs cefixime group.