Nanoclays are layered structures in the nanoscale range with widespread application due to their unique properties such as swelling, cation exchange capacity, and ease of functionalisation using metals, metal oxides, and organic compounds such as carbon paste, polymers, and other biomolecules that form nanoclay composites. Nanoclay functionalisation with silver (Ag), zinc oxide (ZnO), and bimetallic silver–gold (Ag–Au) using hydrophilic and hydrophobic clays is here evaluated and discussed. The composites’ synthesis and morphological, crystallinity, and electroactive properties in comparison with pure nanoclay are also assessed. The layered structure and crystallinity of all these nanoclay composites were slightly changed. The clumped layered structures on the surface of the nanocomposites had dispersed white spots that indicated possible surface modification. The nano-films of the composites’ electroactivity were comparatively high, as seen from the increase in current in the cyclic voltammetry characterisation voltammograms and the differential pulse voltammograms of the pharmaceutical detection. Efavirenz, nevirapine, and zidovudine detection was improved by modification of the nanocomposite with human serum albumin (HSA), as shown by the higher current, thus indicating improved conductivity of the composites compared to the pure nanoclays. Applying HAS-modified nanocomposites in the analysis of efavirenz, nevirapine, and zidovudine on a glassy carbon electrode (GCE) showed good linearity and acceptable detection limits comparable to those of previous studies. Therefore, it has potential for application in pharmaceutical quality control and environmental monitoring.