Bilastine is a second-generation, highly selective H1-receptor antagonist widely used for the treatment of allergic disorders. Beyond conventional antihistaminic activity, its pharmacological profile includes slow H1-receptor dissociation, prolonged receptor residence, and inverse agonism, raising the possibility that H1R modulation may influence inflammatory and tissue responses beyond acute histamine blockade. This review critically evaluates the molecular pharmacology of bilastine and examines emerging evidence for anti-inflammatory and tissue-protective effects, with particular emphasis on the strength and mechanistic limitations of the available evidence. Bilastine has demonstrated suppression of constitutive H1R signaling and attenuation of histamine-dependent responses, while clinical observations suggest reductions in selected inflammatory mediators, including IL-6, IL-8, and IL-17. Experimental evidence further indicates potential renal protection in diabetic nephropathy and favorable epithelial compatibility and wound-repair effects associated with preservative-free bilastine-containing ophthalmic formulations. However, the latter findings cannot yet be attributed specifically to bilastine because formulation components, particularly sodium hyaluronate and the absence of benzalkonium chloride, may substantially contribute to the observed effects. Importantly, direct evidence that bilastine acts as an antioxidant or modulates Nrf2/HO-1, NF-κB, MAPK, mitochondrial homeostasis, or ferroptosis remains insufficient. These pathways therefore represent mechanistic hypotheses rather than established pharmacological actions. Future studies using pathway-specific pharmacological and genetic approaches are needed to determine whether H1R modulation by bilastine causally influences redox homeostasis, inflammation, mitochondrial function, and regulated cell death. Clarifying these mechanisms may define new pharmacological dimensions of H1R antagonism and inform future tissue-protective and translational applications of bilastine.