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Inorganic biopolymer-based nanocomposites are useful for stabilizing lipases for enhanced catalytic performance and easy separation. Herein, we report the operational stability, regenerability, and thermodynamics studies of the ternary biogenic silica/magnetite/graphene oxide nanocomposite (SiO₂/Fe₃O₄/GO) as a support for <i>Candida rugosa</i> lipase (CRL). The X-ray photoelectron spectroscopy (XPS), X-ray diffraction (XRD), field-electron scanning electron microscopy (FESEM), vibrating sample magnetometry (VSM), and nitrogen adsorption/desorption data on the support and biocatalyst corroborated their successful fabrication. XPS revealed the Fe₃O₄ adopted Fe²⁺ and Fe³⁺ oxidation states, while XRD data of GO yielded a peak at 2θ = 11.67°, with the SiO₂/Fe₃O₄/GO revealing a high surface area (≈261 m²/g). The fourier transform infrared (FTIR) spectra affirmed the successful fabricated supports and catalyst. The half-life and thermodynamic parameters of the superparamagnetic immobilized CRL (CRL/SiO₂/Fe₃O₄/GO) improved over the free CRL. The microwave-regenerated CRL/SiO₂/Fe₃O₄/GO (≈82%) exhibited higher catalytic activity than ultrasonic-regenerated (≈71%) ones. Lower activation (<inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><mrow><msub><mi>E</mi><mi>a</mi></msub><mo stretchy="false">)</mo></mrow></semantics></math></inline-formula> and higher deactivation energies (<inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><mrow><msub><mi>E</mi><mi>d</mi></msub><mo stretchy="false">)</mo></mrow></semantics></math></inline-formula> were also noted for the CRL/SiO₂/Fe₃O₄/GO (13.87 kJ/mol, 32.32 kJ/mol) than free CRL (15.26 kJ/mol, 27.60 kJ/mol). A peak at 4.28 min in the gas chromatograph-flame ionization detection (GC-FID) chromatogram of the purified ethyl valerate supported the unique six types of 14 hydrogen atoms of the ester (CAS: 539-82-2) in the proton nuclear magnetic resonance (¹H-NMR) data. The results collectively demonstrated the suitability of SiO₂/Fe₃O₄/GO in stabilizing CRL for improved operational stability and thermodynamics and permitted biocatalyst regenerability.