Regular usage of cosmetic products and drugs in dermatological vehicles may cause irritant contact dermatitis. For example, aluminum chloride (AlCl3), the most efficacious antiperspirant salt to treat hyperhidrosis, shows high irritancy potential. To mitigate the irritant contact dermatitis caused by topical application of products containing AlCl3, we investigated the anti-irritating effects of aloe extract and taurine in vitro and in vivo. In an in vitro experiment, reconstructed human epidermis model, EpiDerm, was tested with AlCl3 in the presence or absence of taurine and aloe extract. In a human clinical study, 12 adult subjects were tested with two products, a commercial AlCl3 antiperspirant product and a prototype 12% AlCl3 formulation containing 0.1% taurine and 0.1% aloe extract. Skin irritation potential in vitro and in vivo was measured by the release of pro-inflammatory cytokine, IL-1α, and chemokine, IL-8. Taurine and aloe extract significantly (p < 0.05) reduced IL-lα and IL-8 production in vitro and in vivo after topical application of formulations containing AlCl3. The blend of taurine and aloe extract demonstrated boosted anti-irritation benefits on AlCl3 irritated skin both in vitro and in vivo. These results suggest that the combination of these anti-irritating actives may possibly be effective in mitigating irritant contact dermatitis caused by other dermatological vehicles containing irritating agents, but further research is warranted to assess their effects.