Molecular chemiluminescence probes with near-infrared (NIR) emission offer promising benefits in deciphering complex pathological processes in a living system, as NIR chemiluminescence minimizes autofluorescence, enhances deep-tissue penetration, and improves signal-to-noise ratio. Molecular engineering using single-luminophore design and dual-luminophore design with intramolecular energy transfer provides ways to develop conventional chemiluminophore scaffolds into NIR chemiluminescence probes with ideal chemiluminescence quantum yield and half-life. By virtue of the structural diversity, 1,2-dioxetane-based NIR chemiluminophores with biomarker activity have been developed. This review summarizes the molecular design strategies of NIR chemiluminescence theranostic probes (NCTPs), followed by introducing activatable NCTPs with their biomedical applications for disease theranostics. Lastly, future perspectives and potential challenges of NIR chemiluminescence imaging in preclinical research and clinical translational potential are discussed.