<p>Pharmaceutical contamination of aquatic ecosystems contributes significantly to antimicrobial resistance, yet conventional wastewater treatment achieves poor removal efficiencies (&lt; 50%) for many antibiotics. This study investigates magnetically recoverable nickel ferrite (NiFe₂O₄) nanoparticles for the photocatalytic degradation of tigecycline (TIG) and fosfomycin (FOS) —two structurally distinct antibiotics belonging to the glycylcycline and phosphonic acid classes, respectively. NiFe₂O₄ nanoparticles, synthesized by co-precipitation and calcined at 750°C, exhibited hierarchical morphology comprising interconnected nanosheets (90–120 nm) and nanoparticles (25–30 nm) with enhanced ferrimagnetic properties (H_c = 1.14 kOe, M_r = 19.8 emu·g⁻¹), enabling efficient magnetic recovery. Systematic optimization identified optimal conditions: 5.0 × 10⁻⁵ mol·L⁻¹ antibiotic concentration, 5 mg.10 mL⁻¹ catalyst loading, and neutral pH. Solar irradiation substantially enhanced performance compared to UV light: at 30 min, solar irradiation achieved 54.8% TIG degradation (vs. 33.7% UV, 1.6-fold enhancement) and 39.7% FOS degradation (vs. 12.1% UV, 3.3-fold enhancement). Mass spectrometry revealed distinct degradation pathways: FOS underwent sequential epoxide ring opening and C–P bond cleavage (m/z 137 → 113.8 → 99.0), while TIG followed side-chain cleavage and aromatic ring oxidation (m/z 586 → 377 → 215). These findings demonstrate the versatility of NiFe₂O₄ photocatalysis for broad-spectrum antibiotic remediation and support the practical viability of solar-driven systems for sustainable water treatment.</p>