Objectives The malondialdehyde (MDA) level and TA count represent the progression of oral potentially malignant disorders (OPMD) to malignancy and thus may be used as an indicator of oral epithelial dysplasia (OED). This study aimed to determine the MDA level and tissue apoptosis (TA) count in oropharyngeal tissue of Wistar rats exposed to sidestream cigarette smoke. Materials and Methods Wistar rats were divided into three groups: T4 group (4-week cigarette smoke exposure), T8 group (8-week cigarette smoke exposure), and control group, which was not exposed to cigarette smoke. The oropharyngeal tissue of the rats from each group was examined histopathologically to count the number of apoptotic cells, and then the blood serum was made to measure the MDA level. Statistical Analysis Bonferroni test was performed to see the differences in each group for MDA level. While the data from tissue apoptosis were analyzed using Mann-Whitney U test for the significance. All data were considered significant if p < 0.05. Results The MDA level and TA count increased as the duration of cigarette smoke exposure increased. In the T8 group, the MDA level and TA count were significantly higher compared with the T4 and control groups with a p-value < 0.05. Conclusions Exposure to sidestream cigarette smoke increased the TA count and MDA level in the oropharyngeal tissue of Wistar rats. The TA count and MDA level may be used as markers of OPMD.