The　persistent　threats　posed　by　toxic　chemical　warfare　agents　(CWAs)　such　as　mustard　gas　(bis(2-chloroethyl)　sulfide,　HD)　and　bacterial　contaminants　demand　the　development　of　innovative,　sustainable　mitigation　strategies.　Photocatalytic　processes　that　generate　reactive　oxygen　species　(ROS)　offer　a　promising　dual-functional　approach　for　both　chemical　detoxification　and　antibacterial　defense.　In　this　study,　two　structurally　analogous　covalent　organic　frameworks　(COFs),　BPY-COF　and　BD-COF,　are　synthesized　using　benzotrithiophene　as　the　donor　unit　paired　with　bipyridine　and　biphenyl,　respectively.　These　COFs　exhibit　high　crystallinity,　broad-spectrum　light　absorption,　and　efficient　charge　carrier　transport,　with　BPY-COF　demonstrating　superior　performance　due　to　the　incorporation　of　heteroatoms.　BPY-COF　achieved　ultrafast　detoxification　of　the　mustard　gas　simulant　2-chloroethyl　ethyl　sulfide　(CEES)　with　a　half-life　of　35 min　and　100%　selectivity　for　2-chloroethyl　sulfoxide　(CEESO)　under　white　LED　light,　outperforming　BD-COF.　Additionally,　electrospun　composite　fibers　containing　40 wt.%　BPY-COF　maintained　comparable　CEES　degradation　rates　and　exhibited　over　99%　antibacterial　efficiency　against　Escherichia　coli　and　Bacillus　subtilis　within　60 min.　These　findings　highlight　the　potential　of　BPY-COF　as　a　multifunctional　photocatalyst　for　integrated　applications　in　chemical　detoxification　and　antibacterial　defense,　addressing　critical　challenges　in　public　health　and　safety.　©　2025　Wiley-VCH　GmbH.