<p>Alzheimer’s disease (AD) poses significant challenges to public health and well-being, with current treatments often providing limited efficacy. <i>Chuanzhitongluo</i> capsule (CZTL) has neuroprotective effects, and is expected to be used for the treatment of AD. In this study, the chemical composition, pharmacological effects and underlying mechanisms of CZTL against AD were systematically investigated. We identified the major components of CZTL through ultra-high-performance liquid chromatography coupled with a quadrupole time-of-flight mass spectrometer. AD rat model was established via scopolamine injection, followed by the administration of CZTL at various dosages, and pharmacological effects were then systematically evaluated. Furthermore, the potential mechanisms were explored using metabolomics and immunohistochemistry. Seventeen chemical constituents were identified from CZTL. Pretreatment with CZTL led to significant improvements in cognitive function and reductions in neuronal loss among AD rats. CZTL administration decreased abnormal protein aggregates (Aβ and Tau), along with markers of oxidative stress and inflammation. Metabolomic and immunohistochemical analyses indicated that CZTL modulated nicotinamide metabolism and impacted levels of NAD+, UMP, nitric oxide, and SIRT1 activity. These results suggest that CZTL effectively mitigates cognitive deficits and neuronal loss in AD by regulating nicotinamide and SIRT1, while inhibiting oxidative stress and inflammation. This study lies in their contribution to the development of novel anti-AD therapies derived from traditional Chinese medicine, paving the way for new approaches in managing neurodegenerative diseases.</p> Graphical abstract <p></p>