Quinazolinones are a class of organic compounds that have attracted significant attention in medicinal chemistry and pharmacology due to their diverse biological activities and potential therapeutic applications. In the present study, a biocomposite, based on cross-linked ionic carboxymethyl cellulose and manganese ferrite (CCMC@MnFe₂O₄), was designed in three steps. The prepared biocomposite was comprehensively characterized using various analytical techniques, including EDX, FESEM, XRD, FTIR, VSM, and TGA instruments. The XRD and FESEM analyses of the CCMC@MnFe₂O₄ revealed a semicrystalline pattern and polyhedral morphology, respectively. The CCMC@MnFe₂O₄ biocomposite was employed as a catalyst for the preparation of quinazolinones. The results showed that quinazolinone derivatives were obtained in high yield (>85%) using 0.07 g of CCMC@MnFe₂O₄ with reaction times ranging from 30 to 60 min in ethanol solvent. CCMC@MnFe₂O₄ could be easily separated from the reaction using a magnet and reused over five consecutive cycles without a significant loss of efficiency. The prepared quinazolinones exhibited antioxidant activity (ranging from 65% to 92%) and demonstrated antimicrobial activity against both E. coli (with an inhibition zone of 7–10 mm) and S. aureus (with an inhibition zone of 8–12 mm). Some of the benefits of this study include a straightforward method, a short reaction duration, a considerable yield, and the ability to reuse and maintain the stability of the catalyst.