Abstract: Objective To investigate the effect of extract of Ginkgo Biloba leaves injection (EGbLI) in inhibiting miR-128-3p on disease progression and inflammatory gene expression in elderly patients with Alzheimer disease (AD). Methods A total of 96 elderly AD patients who were admitted in Xuzhou Central Hospital from October 2022 to October 2024 were enrolled. They were divided into a control group (n=48) and an observation group (n=48) using the random number table method. The control group received conventional Western medicine treatment for AD, while the observation group was additionally administered with EGbLI as a combined therapy, both for 6 months. The Mini-Mental State Examination (MMSE) and Activities of Daily Living (ADL) scores were compared between the two groups before and after 6 months of treatment. The levels of Toll-like receptor 4/nuclear factor-κB (TLR4/NF-κB) signaling pathway molecules and miR-128-3p in peripheral blood mononuclear cells (PBMC) were also compared. The correlation between miR-128-3p expression in peripheral blood and the scale scores and TLR4/NF-κB signaling pathway molecule expression in AD patients was analyzed. During the intervention phase, the incidence of adverse reactions related to treatment was tracked and recorded in both groups. Results After 6 months of treatment, the MMSE scores in the observation group were higher than those in the control group, while the ADL scores were lower (P<0.05). The levels of TLR4 mRNA and NF-κB mRNA/protein in peripheral blood in the observation group were significantly lower than those in the control group (P<0.05). The level of miR-128-3p in peripheral blood in the observation group was significantly lower than that in the control group (P<0.05). Pearson correlation analysis revealed that the expression of miR-128-3p in elderly AD patients was negatively correlated with MMSE scores and positively correlated with ADL scores (P<0.05). The expression of miR-128-3p was positively correlated with the mRNA levels of TLR4 and NF-κB in the TLR4/NF-κB signaling pathway (P<0.05). The incidence of drug-related adverse events in the observation group was not significantly different from that in the control group (P>0.05). Conclusions EGbLI combined with western medicine treatment in elderly patients with newly diagnosed AD helps improve cognitive function and has good safety. The mechanism of its therapeutic effect involves the inhibition of miR-128-3p, leading to a decrease in TLR4/NF-κB signaling pathway activity.