The effect of surface modification by an arc discharge plasma in a nitrogen flow with treatment durations of 5 and 10 min on the physicochemical properties and biocompatibility of the surface of composites based on polylactic acid and hydroxyapatite (PLA/HA) with different mass ratios (80/20, 70/30, 60/40) has been investigated. The aim of this work was to show the correlation between the changes of the physicochemical characteristics (chemical compound, morphology, wettability) of the surface layer of the PLA/HA composites and the cell viability (macrophages) in the presence of the plasma-modified materials. The dependence of alterations of the functional properties (wettability, biocompatibility) on the change in the chemical composition under the plasma exposure has been established. The chemical composition was studied using X-ray photoelectron spectroscopy (XPS), the surface morphology was researched with scanning electron microscopy (SEM), and the wettability of the composite’s surface was analyzed by measuring the contact angle and surface energy calculation. In addition, the viability of macrophages was investigated when the macrophages from three donors interacted with a modified PLA/HA surface. It was found that the formation of the new functional groups, –C-N and N-C=O/C=O, improves the wettability of the surface of the composites and promotes the viability of macrophages in the presence of the composite materials. The fundamental principles for obtaining promising materials with the required properties for eliminating bone defects have been created.