Chemical contaminants in food pose a serious threat to public health, driving the need for sensitive, rapid, and on-site screening methods. Lateral flow immunoassay (LFIA) is rapid and portable but suffers from single-signal readout and insufficient label stability. Nanozymes, nanomaterials with enzyme-like catalytic activity and excellent stability, have emerged as promising signal labels to address these limitations. Moreover, their diverse physiochemical properties enable multiplex signal readout, where two or more complementary signals (e.g., colorimetric, fluorescent, chemiluminescent, photothermal, and surface-enhanced Raman scattering) are generated simultaneously from a single test line. This multiplex strategy significantly enhances detection sensitivity, accuracy, and reliability through signal amplification and self-calibration. This review provides a systematic overview of the catalytic properties and their major types used in multiplex signal LFIA. The signal combination strategies employed in nanozyme-based multiplex signal LFIA were also summarized, and their applications in detecting veterinary drugs, mycotoxins, pesticides, and other food chemical contaminants are highlighted. Ultimately, current challenges and future prospectives in this field are discussed. This review offers guidance for designing high-performance, nanozyme-based multiplex signal LFIA platforms for food safety monitoring.