IntroductionPrimary ovarian insufficiency (POI) is marked by reduced estrogen production and irregular ovulation, often resulting in lowered fertility or infertility. The traditional Chinese medicine "Liu Zi Tang" (LZT) has displayed promising outcomes in treating POI. Yet, conventional oral LZT administration poses challenges, including gastrointestinal irritation and the liver's first-pass effect. Thus, a novel drug delivery approach is imperative. MethodThis research incorporated the extracts of traditional Chinese medicine LZT into a novel liposome type, leading to the creation of LZT-glycerol plasmid/chitosan hydrogel (LZT-Gly-Lip/CS Gel) drug-carrier patches for achieving transdermal gradual-release drug delivery. The POI model was established in rats through intraperitoneal injection of vinylcyclohexene dioxide (VCD). A total of twenty-four 4-week-old female SD rats were distributed randomly among four groups: negative control (NC), vinylcyclohexene dioxide model (VCD), LZT/chitosan hydrogel treatment (VCD+LZT/CS Gel), and LZT glycerol liposome/chitosan hydrogel treatment (VCD+LZT-Gly-Lip/CS Gel). The therapeutic efficacy was evaluated by observing and analyzing the rats' body weight, diverse organ indices, serum hormone levels, and histopathological sections. ResultRats treated with LZT-Gly-Lip/CS Gel manifested significant enhancements in body weight (243.0 ± 11.0 g), serum estradiol concentration (64.362 ± 6.461 pg/mL), and uterus index (0.34 ± 0.05 %), demonstrating outcomes approaching normal levels (245.3 ± 12.0 g, 74.280 ± 8.903 pg/mL, 0.32 ± 0.10 %, respectively). DiscussionThese results confirm the effectiveness of LZT-Gly-Lip/CS Gel as a promising transdermal drug delivery system for addressing POI.