Based on zinc oxysulfides, quaternary semiconductors MZnOS (M = Ca, Ba, Sr, or other metals) are gaining attention as host materials for luminescent dopant ions. While these materials have been applied in various piezoluminescent devices, their biocompatibility has been scarcely investigated. In this study, yellow-to-red emitting triboluminescent powders of Mn²⁺-doped CaZnOS and BaZnOS (CaZnOS:Mn²⁺ and BaZnOS:Mn²⁺) were synthesized via solid-state reaction. They were studied with a focus on their optical properties and, critically, biocompatibility. Both compounds exhibit photoluminescence (PL) and mechanoluminescence (ML) emissions of Mn²⁺ ions, characterized by a single broad band spanning 550–700 nm. The PL emission peaks at 587 nm (yellow light) of CaZnOS:Mn²⁺ and 623 nm (red light) of BaZnOS:Mn²⁺, irrespective of excitation wavelength. Conversely, the ML emission for both …