This study highlights a simple and efficient nanochemistry-based approach for the effective degradation of triphenylmethane and toxic dye, malachite green (MG) using Argon cold plasma-modified cobalt oxide nanoparticles (Ar-Co3O4-NPs). Synthesized particles were characterized using scanning electron microscope, X-ray diffraction, and Fourier-transform infrared spectroscopy. The peroxidasemimic activity of Co3O4-NPs was evaluated, and the results confirmed that the catalytic activity of Co3O4-NPs was enhanced after plasma modification. The decomposition of MG was tested using the improved catalytic activity of Ar-Co3O4-NPs in model aqueous solution. The results indicated the ability of 0.16 g/mL Ar-Co3O4-NPs to completely degrade 40 lM MG within 70 min with a decolorization efficiency of 96.78%. Experimental conditions were optimized for maximum MG removal. Gas chromatography-mass spectrometry was used to determine the byproducts of MG degradation, and the findings indicated the production of less toxic products. The toxicity of the resultant metabolites of MG degradation was evaluated against E. coli and B. subtilis and the results confirmed less toxic product formation. Artificial neural networks (ANNs) were used to model the catalytic degradation data, and the strong correlation between experimental observations and ANN model predictions suggested that the designed model could accurately predict MG dye removal efficiency under different operating conditions.