There is an urgent need for exploring reliable and low-cost techniques for simultaneous detection of neurological drugs to facilitate timely diagnosis and treatment of various neurological disorders. In this work, we demonstrate a low cost, one-step synthesis of spinel magnesium aluminate (MgAl2O4) nanoparticles as a chemically stable substrate for rapid, simultaneous detection of neurological drugs like nicotine, gabapentin, caffeine and carbamazepine in the biofluids via surface-enhanced Raman scattering (SERS) technique. The substrate exhibits a limit of detection (LOD) of 0.18 ng/mL, 0.78 μg/mL, 0.1 μg/mL and 0.81 μg/mL with an enhancement factor (EF) of 1.61 × 107, 9.70 × 107, 7.72 × 107 and 1.52 × 107 towards detection of nicotine, gabapentin, caffeine and carbamazepine, respectively with an accumulation time of 20 s. The substrate exhibits an excellent selectivity and a wide dynamic range of detection towards the drug molecules in presence of 0.1 mM of ascorbic acid (AA), NaCl, KCl, CaCl2, urea, and glucose. This excellent performance can be ascribed to the interaction between the metallic sties of the MgAl2O4 cubic spinel structure and the drug molecules which leads to the resonance Raman scattering-like effect through the reconstruction of the energy bandgap closer to the photon energy of the excitation laser. Simultaneous recognition of drug molecules in the blood serum samples with reliable recovery percentages is also achieved using this platform thus, proving its efficacy for developing perovskite materials-based SERS detection useful in bioanalytical applications. © 2022 Elsevier Ltd and Techna Group S.r.l.