Bacterial plaque is solely responsible for the initiation and progression of periodontal diseases. There are different mechanical and chemical methods available for the maintenance of oral health through plaque control. Toothbrushes and miswak (chewing sticks) are widely used for the mechanical removal of plaque. Chlorhexidine gluconate (CHX) is one of the best-proven anti-plaque agents. The aim of this study was to evaluate the effects of CHX and miswak extract on healthy and periodontally involved human dentin. Sixteen human premolars recently extracted for orthodontic and periodontal reasons were used in the study. Teeth were free from caries, cervical restorations, or erosions. The dentin disc specimens were prepared and half of them were etched with 6% citric acid for 120 sec. Both etched and unetched were further treated with CHX and 50% miswak extract and prepared for Scanning Electron Microscopic (SEM) examination. It was concluded that CHX 0.2% and miswak extract 50% had a similar effect on dentin in the control group. Miswak extract removed more smear layer as compared to CHX. Further research is needed in vivo to compare the effects of CHX and miswak extract on periodontally involved teeth and teeth with dentinal hypersensitivity.