Background: Topical minoxidil remains the only FDA-approved treatment for hair loss, yet its clinical efficacy is compromised by organic-solvent-induced scalp irritation and poor patient adherence. This study aimed to evaluate natural illite as a carrier for minoxidil and to explore its potential hair-growth-promoting mechanisms. Methods: Thermal–acid-modified illite was engineered as a spray-dried, hydroalcohol-free minoxidil carrier for topical application. Hair regrowth efficacy was assessed in C57BL/6 mice via a 14-day depilation model. Mechanisms were elucidated via RNA-seq, Ki67/TUNEL immunofluorescence, and p-STAT3 immunohistochemistry. Results: Modified illite resulted in a 4.2-fold surface area increase and successful minoxidil loading. The minoxidil/illite formulation demonstrated efficacy equivalent to that of free minoxidil while also eliminating solvent toxicity. Mechanistic analysis revealed that illite functions as an active carrier: both the illite-alone and minoxidil/illite-treated groups exhibited increased Ki67⁺ proliferation and reduced TUNEL⁺ apoptosis. Transcriptomic profiling demonstrated dual mechanisms—enrichment of Myc proliferation pathways and suppression of IL-6 inflammatory signaling (p < 0.001)—with reduced p-STAT3 expression confirmed by immunohistochemistry. Conclusions: These findings suggest that an illite-based carrier can enable topical delivery of minoxidil with preserved efficacy and that illite itself exhibits intrinsic hair-growth-promoting activity via anti-inflammatory and pro-proliferative mechanisms, which may help alleviate adherence barriers associated with conventional topical alopecia therapy.