Background: Diabetes and its associated complications take a toll on the elderly. It is known that medication burden could reduce patients’ adherence, which in turn impacts negatively on the health-related quality of life (HRQOL) of those suffering from chronic diseases. Studies have been conducted on HRQOL and its associated factors among diabetic patients but none has studied pill burden effects on HRQOL. This research evaluated pharmacist’s intervention on pill burden effects on the HRQOL of elderly diabetic patients. Methods: This 8-month randomized controlled study involved 170 elderly type 2 diabetic patients. Socio-demographics, the impact of the number and dosage frequency of drugs on adherence, and the influence of the pill burden on HRQOL scores were evaluated at baseline and at 4 and 8 months. Patients in the intervention group were educated about diabetes and its management and counselled on treatment adherence. Brisk walking was specially demonstrated to them at least 4 times during the study period. The control group received only the usual call reminders for appointment days. Results: At baseline, 58.8 and 64.7%, respectively, in the control and intervention groups responded “yes” (indicating a negative effect on their adherence) to >5 pills per prescription, while the figures were 55.3 and 15.3%, respectively, at 8 months ( p = 0.711 and p = 0.000, respectively). Patients on 1–5 pills per prescription in the control group had the following physical functioning scores: baseline (44.2 ± 14.2) versus 4 months (47.2 ± 19.1) and 8 months (47.7 ± 16.1); p = 0.277 and p = 0.160. The physical functioning scores in the intervention group were: baseline (41.7 ± 16.1) versus 4 months (67.6 ± 23.1) and 8 months (92.5 ± 3.5); p ≤ 0.001. The same pattern of results was found for those on >5 pills per prescription. Conclusion: This study demonstrates pharmacists’ ability to improve the HRQOL of patients through continuous counselling, supply of relevant information, and monitoring of drug, exercise, and diet adherence. Intervention such as this could be beneficial to diabetic patients and others with chronic diseases.