Adverse drug interactions (ADIs) remain a prevalent issue in hospital settings, highlighting the critical role of pharmacists in their prevention and management. This study aims to assess the knowledge, attitudes, and practices of hospital pharmacists in South Sulawesi Province, Indonesia, concerning clinically relevant drug interactions. Using a cross-sectional design, an online questionnaire was distributed to hospital pharmacists from November 2023 to January 2024. Among the 312 participants, we found that 38.8% had low, 31.4% had moderate, and 29.8% had high knowledge of drug interactions. Most of the pharmacists (94.5%) used software to evaluate drug interactions, and a significant proportion (91%) emphasized the necessity for regular training. Additionally, pharmacists routinely screened prescriptions for potential interactions (94.5%), assessed risks before dispensing (91.7%), documented drug interactions (85.3%), provided patient counseling (89.4%), and contacted prescribing physicians when necessary (91%). Despite the identified gaps in knowledge, the alignment of pharmacists’ practices with standard procedures for managing drug interactions highlights their proactive approach to patient safety. This research underscores the need for targeted educational initiatives and continuous professional development to enhance pharmacists’ understanding of drug interactions, ultimately improving patient outcomes in South Sulawesi, Indonesia.