This study aims to develop an efficient and eco-friendly acrylic-based varnish reinforced with nanoparticles (AVRN) to protect the surfaces of historical oil paintings against light and biodeterioration.Simulated mock-ups (SMs) were used to assess the AVRN, which integrated 5% and 1% nanomaterial (SiO2/TiO2) with 7% acrylic varnishes (Paraloid B72/Plexisol P550) in toluene. X-ray Diffraction (XRD) and Transmission Electron Microscopy (TEM) were used in the characterization of the nanomaterials. SMs were prepared using celadonite, lemon yellow, and ivory black pigments in linseed oil, then thermally aged and treated with four formulas (F1, F2, F3, and F4) of the AVRN. A set of the AVRN-treated SMs was infected by UV-O3, and another set was aged by P. aeruginosa, B. cereus, and A. flavus. SEM, TEM, colorimeter, and inhibition zone were used to assess the efficiency oftreatments. The obtained results revealed that the four formulas of the AVRN improved the properties of the treated SMs tovarying degrees. The F4 (SMs treated with TiO2-NPs 1% suspended in Plexisol P550 7%) showed the optimum results, and the F4-treated SMs demonstrated superior stability under UV-O3 and microbial aging. Finally, TiO2-NPs 1% showed better results than SiO2-NPs 5%, ivory black showed better stability than celadonite and lemon yellow against aging factors, and Plexisol P550 gave better results in protecting oil painting surfaces than Paraloid B72 at the same concentration. The study recommends the application of the TiO2-NPs 1% suspended in Plexisol P550 7% for protecting the surfaces of historical oil paintings against light and biodeterioration