The goal of this retrospective research was to assess the root and root canal morphology of mandibular premolars in the Egyptian population using cone-beam computed tomography. 300 CBCT scans were surveyed and the anatomy of 306 mandibular first and 288 second premolars was evaluated. The prevalence of the number of roots, root canals, canal morphologies according to the Vertucci classification and C-shaped canals was calculated and statistically assessed. Regarding the first and second mandibular premolars, the majority showed 1 root (95.4% and 98.6%, respectively) with 1 canal (84.6% and 97.9%). Most of the mandibular first (62.4%) and second premolars (96.2%) showed (type I) root canal morphology, followed by type V (27.1% and 2.1%) in the first and second premolars, respectively. A C-shaped root canal configuration was only detected in one mandibular second premolar (0.3%). Additional root canals and variations in root canal morphology should be considered when treating mandibular premolars to avoid failures.