Objective: To explore the effects of scalp cluster acupuncture on neuroinflammation and the Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) signaling pathway in amyloid precursor protein/presenilin 1 double transgenic (APP/PS1) mice. Methods: 18 male APP/PS1 transgenic mice were randomly divided into model group and scalp cluster acupuncture group, with 9 mice in each group, and 9 age-matched C57BL/6 mice were selected as the blank control group. Mice in the scalp cluster acupuncture group received acupuncture once daily at Baihui (GV20) and two points 2 mm lateral to the left and right of Baihui for 28 consecutive days. Morris water maze was used to evaluate learning and memory ability of mice. Nissl staining was used to observe the number of hippocampal neurons. Enzyme-linked immunosorbent assay (ELISA) was used to detect serum levels of interleukin-6 (IL-6), interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α). Western blot was used to analyze the expression of JAK2, p-JAK2, STAT3 and p-STAT3 proteins in the hippocampus. Results: Compared with the blank control group, the escape latency of mice in the model group was prolonged, and the number of platform crossings and the time spent in the target quadrant were reduced (P<0.01), the number of hippocampal neurons was decreased (P<0.01), serum levels of IL-6, IL-1β and TNF-α were increased (P<0.01), and the protein expression levels of p-JAK2 and p-STAT3 were increased (P<0.01). Compared with the model group, cognitive function of mice in the scalp cluster acupuncture group was improved (P<0.05), the number of hippocampal neurons was increased (P<0.01), serum levels of IL-6, IL-1β and TNF-α were decreased (P<0.01), and the protein expression levels of p-JAK2 and p-STAT3 were decreased (P<0.01). Conclusion: Scalp cluster acupuncture may inhibit neuroinflammatory responses by regulating the JAK2/STAT3 signaling pathway, thereby improving cognitive function in APP/PS1 mice.