Aims and objectives Mechanical debridement using subgingival Scaling and Root Planning (SRP) can unequivocally be considered a well-established and effective method for non-surgical treatment of periodontitis. The objective of the present study was to assess the clinical efficiency of Full Mouth Scaling (FMS) and Full Mouth Disinfection (FMD) compared to Quadrant-wise Scaling and Root Planing (Q-SRP) in patients with periodontitis. Materials and methods A randomized clinical trial was conducted among 180 patients having periodontitis. The patients were randomly divided into three treatment groups. Group I received Full Mouth Scaling (FMS), Group II received Quadrant-wise Scaling and Root Planning (Q-SRP), Group III received Full Mouth Disinfection (FMD). Assessment of clinical parameters was done at baseline and 3 months. Results Intragroup analysis revealed a statistically significant difference among all three groups from baseline to three months (p ≤0.05). Intergroup comparisons revealed no significant differences in terms of Probing Pocket Depth (PPD) and Clinical Attachment Level (CAL) among the three groups. During the study period, Plaque Index (PI) and modified Sulcus Bleeding Index (mSBI) changes were reduced significantly in Q-SRP compared to the other two groups. Operator fatigue was comparatively less in Q-SRP compared to FMS and FMD. Conclusions The presented results depict the short-term effects. All three treatment modalities showed improvements in clinical parameters after three months. Each of the three treatment strategies shows effectiveness and can be recommended for managing severe chronic periodontitis.