<p>Microneedle patches, which are minimally invasive and have high patient compliance, offer a potential alternative for transdermal drug delivery, particularly in chronic diseases such as osteoporosis, which require consistent long-term therapy. Genistein is an osteoprotective plant-derived isoflavone that suffers from poor aqueous solubility and low bioavailability, thereby limiting its medicinal value. In this study, a genistein-loaded solid lipid nanoparticles integrated with dissolving microneedles was developed for the management of osteoporosis. SLNs were prepared using glyceryl monostearate and Tween 80, and optimized by using a Box-Behnken design. The optimised formulation of SLNs (F3) was incorporated into dissolving microneedles. The developed dissolving microneedles were studied for various characterisations, and they featured uniform geometry, sharp, pointed edges, a drug delivery profile of 69.218 ± 3.64% at 8&#xa0;h. Its anti-osteoporotic studies were carried out on 6 groups of Wistar albino rats, and studies showed that significant decrease in the creatinine level and osteoclast cells; on the other hand, a substantial increase in total protein, bone weight, hardness, thickness, and trabecular composition. A skin irritation test, which was performed, manifested the biocompatible, dermatologically safe quality of the developed dissolving microneedles. This microneedle platform, coupled with an optimised SLNs carrier, ensures a non-invasive controlled transdermal delivery, maximising genistein's osteogenic potency for the effective management of osteoporosis.</p> Graphical Abstract <p></p>