Background: The term sexually transmitted infection (STI) is used to denote a variety of clinical conditions that caused by pathogens that can be acquired and transmitted through sexual activity. The problem with most STDs is that they can occur symptom-free and can thus be passed on unaware during unprotected sexual intercourse. Sexually transmitted diseases are a major health problem affecting mostly young people, not only in developing but also in developed countries. Over the period 1985-1996, a general decrease in gonorrhea, syphilis, and chlamydia infections was noted in developed countries, both in the general population and among adolescents [1]. Objective: The aim was to assess Nurses' Knowledge and Practice regarding Sexually Transmitted Diseases at 250 Bedded Bangamata Sheikh Fazilatunessa Mujib General Hospital, Sirajganj. Methodology: This descriptive cross-sectional study design was used, and a sample size of 110 was a simple random sampling technique followed by those who met the inclusion criteria to assess the nurse's Knowledge and Practice regarding Sexually Transmitted Diseases. The study was conducted from July 2021 to December 2021. The instruments for data collection were a semi-structured questionnaire, which is composed of three parts: Demographic variables, knowledge, and practice-based information on Sexually Transmitted Diseases. Results: The findings of the present study revealed that the demographic characteristics of the highest 51.82% were within 31-40 years; 80.91% were female; 80.91% were Muslim; 59.09% were married; 60% were diploma in nursing and average knowledge score 41.82% were high level of knowledge regarding the Sexually Transmitted Diseases. Conclusion: The present study concluded that the level of nurses' knowledge regarding sexually transmitted diseases was 41.82% high level of knowledge regarding STDs in the current study, which may be due to their professional and clinical experiences. In addition to knowledge regarding STDs, prevention is very important for Bangladeshi people.