This paper presents a facile approach to develop palygorskite (Pal), a fibrous clay mineral, as a delivery system of tea tree oil (TTO) for topical acne therapy. The obtained TTO-Pal composite showed an efficient loading of TTO (27.4%) with a selective accumulation of terpine-4-ol and 1,8-cineole (two major antimicrobial TTO constituents), sustained release of TTO at skin physiological conditions (pH5.4, 32 °C) and superior skin sebum (2.2 g/g) absorbability. In vitro toxicological assessments showed that the Pal incorporation strategy significantly reduced the acute contact toxicity of TTO. The antimicrobial results revealed a preferable bacteriostatic effect for the TTO-Pal system towards opportunistic dermal pathogens (Escherichia coli, Staphylococcus aureus and Propionibacterium acnes) over the beneficial bacterium (Staphylococcus epidermis). Moreover, TTO-Pal based formulations exhibited pronounced clinical therapeutic efficacy in treating facial acne by rapidly reducing inflamed lesions, modulating skin sebum overproduction and restoring barrier function. This is the first report of using fibrous clay as a biocompatible nanocarrier system for topical delivery of essential oils in efficient management of facial acne with both in vitro and in vivo evidences, which may open perspectives for fibrous clay-drug delivery system in topical application and expand the high added value development of this mineral resource in the advanced healthcare fields.