Background: While clinical pharmacists are expected to have a potential role in minimizing prescribing errors (PEs) in patients with diabetes, the effectiveness of their interventions on the incidence and clinical significance of PEs remains unclear. Objectives: To investigate the effectiveness of clinical pharmacist interventions in correcting PEs in diabetic patients with major polypharmacy. Methods: This was a prospective pre-post study conducted in a secondary care hospital in Jordan over 4 months. There were 2 phases: Control, in which PEs were identified and categorized and active, in which clinical pharmacists intercepted and corrected PEs. Clinical severity of prescribing incidents was evaluated by an expert panel, comprising a senior clinical pharmacist, an internist, and cardiologist. SPSS V26 was used for data analysis. Results: Of 928 patients, 432 were followed and reviewed during the control phase and 496 during the active phase. Clinical pharmacist interventions reduced PEs by 89.5%; from 27.6% (control) to 2.9% (active). PEs per patient and PEs per medication orders were reduced from 2.1 to 0.2 and from 0.3 to 0.03, respectively. Electronic selection errors, wrong dose frequency, duplicate drugs, and allergy errors disappeared in the active phase. Significant, serious, and lethal errors were significantly reduced from 35.4%, 11.6%, and 0.2% (control) to 13.5%, 3.1%, and 0.0% (active), respectively. drugs related to CVS (OR = 5.2; 95% CI, 3.1-8.6; P < .05) versus drugs related to endocrine system was more likely to be associated with the occurrence of PEs versus no PEs. However, drug belonging to infectious (OR = 0.6; 95% CI, 0.1-0.9; P < .05) versus drugs related to endocrine system was less likely to be associated with the occurrence PEs versus no PEs. Conclusion: Clinical pharmacist interventions significantly reduced PEs in patients with diabetes by 89.5% and most of these interventions were clinically significant.