Background: Diabetic foot ulcer is the most common foot injury leading to lower extremity amputation, which is preventable through proper education on foot care practice. Objective: To assess the effectiveness of Self Instructional Module (SIM) on knowledge regarding prevention of diabetic foot ulcer. Material and method: A pre experimental one group pre test post test design is used with 102 samples from Medicine, Endocrinology and Nephrology Ward of Gauhati Medical College Hospital, Guwahati using convenient sampling technique. Demographic Performa, clinical datasheet and structured knowledge questionnaire were administered followed by distribution of Self Instructional Module (SIM) on knowledge regarding prevention of diabetic foot ulcer. The post test was conducted after a week. Data were analyzed by using the software package SPSS 20 version. Results: In pre test, 77 (75.5%) sample had average knowledge, whereas, in post test, 102(100%) had good knowledge regarding prevention of diabetic foot ulcer. The mean post test knowledge score (23.44) was higher than the mean pre test knowledge score (9.61). The‘t’ value [t101= (–) 47.06 at df=101 p<0.05] was highly significant at 0.05 level of significance. There was significant association of knowledge regarding prevention of diabetic foot ulcer with demographic variables with respect of educational status. However, there is no significant association of knowledge regarding prevention of diabetic foot ulcer with selected clinical variables. Conclusion: The study revealed that, Self Instructional Module (SIM) was effective in improving the knowledge regarding prevention of diabetic foot ulcer.