Smart lockers are automated delivery machines. They have been used in dispensing ARVs and Tuberculosis medication to chronically ill patients in South Africa, Kenya, and Eswatini. However, there is no evidence of smart lockers in dispensing chronic disease medication in Nigeria. This study aimed to assess the acceptability of smart lockers in dispensing chronic disease medication and to describe the barriers to accessing care among patients with chronic diseases medication in 5 states in Nigeria. We conducted a cross-sectional study among healthcare workers and patients living with chronic diseases in five Nigerian states of Adamawa, Akwa Ibom, Cross River, Benue, and Niger between November and December 2021. A total of 1,133 participants were recruited (728 patients and 405 healthcare workers). The results revealed that most patients and healthcare workers agreed that using smart lockers for drug dispensing will lead to reduced transportation costs, hospital waiting times, the workload of healthcare workers, and decongestion of health facilities. The majority of the patients living with chronic diseases (43%) and healthcare workers (51%) showed high acceptability for the use of smart lockers. The use of smart lockers in dispensing chronic disease medication in Nigeria is feasible, and patients and healthcare workers are willing to accept the smart lockers, provided that a patient-centred implementation strategy is developed.