Three eco-friendly and cost-effective analytical methods were developed and optimized for quantitative analysis of some veterinary drug residues in production wastewater samples. The studied drugs were ivermectin, rafoxanide and sulfadimidine. A solid-phase extraction procedure was employed using Bond Elut C18 cartridges, prior to analysis. The first method was a chemometric approach called multivariate curve resolution – alternating least squares (MCR-ALS). A calibration model was developed and several figures of merit (RMSEP, SEP, bias, RE%) were calculated. The second method was a thin layer chromatography followed by densitometric measurements at 245 nm. The separation was performed using silica gel 60 F₂₅₄ plates and ethyl acetate : acetonitrile : toluene : ammonia (20 : 3 : 2 : 1, by volume) as a developing system. The third method was a high performance liquid chromatographic separation on HiQsil C18 HS column with UV detection at 245 nm. The mobile phase consisted of acetonitrile : methanol : water (60 : 25 : 15, by volume), with a flow rate of 1.5 mL min⁻¹. The proposed methods were validated according to ICH guidelines. The described procedures were applied to quantify the studied drug residues in synthetic and real industrial wastewater samples. The proposed methods were statistically compared with the official and the reported methods, showing no significant difference with respect to accuracy and precision at P = 0.05.