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Objective To assess healthcare professionals’ knowledge, attitudes, and practices (KAP) towards deprescribing.Design A facility-based cross-sectional study was conducted from May to June 2025.Setting Two public hospitals in Gondar, Ethiopia.Participants A total of 389 healthcare professionals participated in this study with a 92.2% response rate.Outcomes We assessed healthcare professionals’ KAP towards deprescribing as the primary outcomes. These were measured using a structured, self-administered questionnaire.Results The majority of participants were female (54.2%), and the largest age group was 21–28 years (46.0%). The study revealed that most of the study participants were nurses (65.6%), with most (88.7%) graduating from government institutions. The overall proportion of participants with good knowledge of deprescribing was 32%, while 51.7% had a positive attitude and 27.2% demonstrated good practice. The multivariable analysis revealed that male participants (AOR=2.866, 95% CI 1.734 to 4.737), graduating from a governmental institution (AOR=2.895, 95% CI 1.244 to 6.736) and being a pharmacist (AOR=4.115, 95% CI 1.678 to 10.090) were also positively associated with good knowledge.Conclusions Among the participants, nearly half (49%) of healthcare providers demonstrated poor knowledge of deprescribing, while more than half (53.3%) showed poor practice. Overall, the study highlights that healthcare professionals have limited awareness of deprescribing. Therefore, deprescribing should be incorporated into undergraduate curricula and training should be provided for healthcare professionals.