Using ClO4− anion, the X− counter ions of the monocation [CuX (phen)2]. X complexes (X = Br, Cl, and NO3) have been nucleophilically substituted resulting in three new ClO4−/X− hybrids [CuX (phen)2].ClO4 salt complexes 1–3 for their structural and pharmacological purposes. This substitution reaction is being monitored by IR, UV–Vis, and EDX. Moreover, the desired hybrid complexes 1–3 were analyzed using a wide variety of analytical tools, such as EDX, X-ray, MS, FT-IR, UV–Vis., SEM, CHN-EA, and TG/DTG. Both complex 1 and complex 2 showed a high distortion square pyramid (DSP) structure centered on Cu(II) when X-ray diffraction was performed, XRD/HSA-interactions reflected the existence of several synthons mainly formed via Cph-H ….OClO3 H-bond interactions. The complexes with the most stable thermal behavior were reflected by the TG/DTG; meanwhile, only two steps of degradation were recorded. All the complexes showed high activity against eight types of bacteria strains; in most cases, the complexes were more active than the Gentamicin universal antibiotic. Additionally, the complexes' inflammation ability via cyclooxygenase (COX) and lipoxygenase (LOX) enzyme inhibitions have been recorded, and then the molecular docking using suitable enzymes was served to explain the experimental anti-inflammatory results.