INTRODUCTION: The urea composition has a profound effect on skin disorders, specifically xerosis, desquamation, and scaling, which are some of the main concerns of the current health industry. The application of urea is relatable and more bioactive than alternate treatments. The objective of this systematic review was to evaluate the effectiveness of topically applied urea in the treatment of ichthyosis, psoriasis, and other dermatologic conditions. DATA AND SOURCES: Research articles were retrieved through electronic databases, including Google Scholar, PubMed, EMBASE, Elsevier, and Sage, selected based on the provision of online free literature from its inception till November 2023. The significant findings were skin dryness, transepidermal water loss (TEWL), and eczema. STUDY SELECTION: A total of 1826 studies have been found, of which 31 were selected based on inclusion criteria. The primary reason for the exclusion of the studies was the application of urea as a control. All in vivo studies disclosed the effectiveness of urea treatment separately or in addition to another compound on skin conditions. The selected studies have reported findings related to the improvement in xerosis, erythema, scaling, and reduction in TEWL. CONCLUSION: According to the in-depth review of the research articles, the application of urea has a tremendous effect on different skin diseases. Still, its role as monotherapy is overlooked due to the presence of more susceptible alternate products that need to be addressed. However, in the future, the evaluation of the effects of treatment containing urea with antibiotics on skin diseases would be more beneficial for practical knowledge.