The purpose of this study was to fabricate non-invasive transdermal patches loaded with promising greenly synthesized nanoparticles for breast cancer therapy. The half maximum inhibitory concentration (IC50) on triple negative breast cancer (TNBC) and human dermal fibroblast (HDF) cell lines were investigated. In addition, the migration inhibition of the cancerous cells was investigated as well. Moreover, the physicochemical properties (water uptake, thickness, weight, and content uniformity) of the patches were evaluated with the in-vitro release of the prepared nanoparticles from the patches. Carbopol was used as a film forming polymer, ethylene-vinyl acetate as a backing layer, while the root hair extract of Phoenix dactylifera was used as a reducing agent to form zinc oxide nanoparticles (ZnO NPs). Clear, transparent, and flexible transdermal patches were successfully synthesized with uniform thickness (0.25 +/- 0.001 mm) and weight (0.42 +/- 0.007 g). Patches showed ZnO NPs content uniformity of 91.74-94.40% with surface pH of 6.25 +/- 0.02. They exhibited sustained release of ZnO NPs over 25 h with a steady-state flux of 7.21 mu g/h/cm(2). The particle size of ZnO NPs was 88.15 +/- 4.99 nm, polydispersity index was 0.44 +/- 0.26, and zeta potential was - 16.63 mV. Moreover, the cytotoxicity of ZnO NPs on the TNBC cell lines was dose dependent. Accordingly, it increased from 54 to 100% upon increasing ZnO NPs concentration from 0.16 to 2.5 mu g/mL. The IC50 of ZnO NPs (0.42 mu g/mL) on TNBC was significantly (p < 0.05) less than the IC50 of doxorubicin (4.58 mu g/mL), and the IC50 of ZnO NPs on HDF (1.61 mu g/mL). Thus, this non-invasive patch demonstrated stronger efficiency of ZnO NPs in inhibiting cancerous cells' growth as opposed to doxorubicin, and low toxicity on normal cells. Hence, it may offer a potential transdermal delivery to resolve the limitations of invasive chemotherapy delivery.