It has been observed that increased accumulation of Aβ peptides in the brain triggers endogenous oxidative stress, neuroinflammation, and memory dysfunction in Alzheimer’s Disease (AD). Crataegus pinnatifida Bge. Commonly referred to as the Hawthorn leaf is a well-known traditional Chinese medicine. The plant is used for conditions such as hyperlipidemia, heart palpitations, forgetfulness, and tinnitus in mainstream medicinal practice, where the most important bioactive components consist of Hawthorn Leaf Flavonoids (HLF). Xu and associates showed that in a rat model given Aβ25-35 (bilateral hippocampus injection), the neuroprotective effects of HLF were significant. Oral doses of 50, 100, and 200 mg/kg for a time period of 30 days of HLF demonstrated significant attenuation of the damage to neurons alongside marked inhibition in memory deficits. Enhancement in the enzyme activities of superoxide dismutase and catalase, and glutathione content was seen. In contrast, HLF decreased the malondialdehyde content in the Aβ25-35 rat AD model and suppressed astrocytes’ activation, ameliorating neuroinflammation. HLF upregulated NQO-1, Nrf-2, and HO-1 protein expressions. These results demonstrated the potential of HLF as a potential AD therapeutic. Phytother Res (2022) DOI: 10.1002/ptr.7690.