In recent years, microneedles (MNs) have emerged as a promising alternative to traditional drug delivery systems in transdermal drug delivery. The use of MNs has demonstrated significant potential in improving patient acceptance and convenience while avoiding the invasiveness of traditional injections. Dissolving, solid, hollow, coated, and hydrogel microneedles are among the various types studied for drug delivery. Dissolving microneedles (DMNs), in particular, have gained attention for their safety, painlessness, patient convenience, and high delivery efficiency. This comprehensive review primarily focuses on different types of microneedles, fabrication methods, and materials used in fabrication of DMNs such as hyaluronic acid, chitosan, alginate, gelatin, collagen, silk fibroin, albumin, cellulose and starch, to list a few. The review also provides an exhaustive discussion on the applications of DMNs, including the delivery of vaccines, cosmetic agents, contraceptives, hormone and genes, and other therapeutic applications like for treating cancer, skin diseases, and diabetes, among others, are covered in this review. Additionally, this review highlights some of the DMN systems that are presently undergoing clinical trials. Finally, the review discusses current advances and trends in DMNs, as well as future prospective directions for this ground-breaking technology in drug delivery.