Background: This study investigated the impact of repetitive transcranial magnetic stimulation (rTMS) on serum levels of Amyloid-β (Aβ) as well as the ectodomain of p75 neurotrophin receptor (p75ECD) in patients with Alzheimer's disease (AD). Methods: A total of 46 patients diagnosed with AD between June 1, 2020 and December 31, 2021 were randomized to undergo either 20 Hz rTMS treatment of the left dorsolateral prefrontal cortex (DLPFC) or sham procedure. Cognitive function and activity of daily living were evaluated. Neuropsychological tests and blood samples were gathered at baseline and at 2, 3, 4, and 6 weeks after rTMS therapy. Results: There were no evident differences between rTMS group and sham group in serum Aβ40, Aβ42, total Aβ, ApoE, and p75ECD standards at baseline (p > 0.05). Serum levels of Aβ40, Aβ42, as well as total Aβ, were significantly lower in the rTMS group at 3, 4 and 6 weeks relative to the sham group (p < 0.05). Serum p75ECD levels in the rTMS group were significantly higher than those of the sham group at 3, 4 and 6 weeks (p < 0.05). Levels of serum Aβ40 (r: -0.78, -0.83, -0.68, respectively), Aβ42 (r: -0.76, -0.76, -0.61, respectively) and total Aβ (r: -0.74, -0.81, -0.66, respectively) were negatively correlated with MoCA, MMSE and MBI scores, while serum p75ECD levels (r: 0.84, 0.90, 0.72, respectively) were positively correlated (p < 0.01). The level of serum Aβ40 (r = 0.77), Aβ42 (r = 0.69) as well as total Aβ (r = 0.73) were positively correlated with ADAS-cog score, while p75ECD levels (r = -0.86) were negatively correlated (p < 0.01). Conclusions: The results of this study suggest that rTMS may decrease serum Aβ levels and increase serum p75ECD levels in patients with AD, offering insight into a potential underpinning mechanism of rTMS.