Background/Objectives: Banisteriopsis caapi contains β-carboline alkaloids with neuropharmacological and immunomodulatory properties, but their effects during prolonged exposure in established amyloid pathology remain poorly characterized. This study investigated whether chronic intermittent B. caapi administration modifies behavioral performance, fibrillar amyloid pathology, and hippocampal microglial alterations in aged PDGFB-APPSwInd mice. Methods: Male wild-type (WT) and PDGFB-APPSwInd transgenic (TG) mice aged 15–18 months received B. caapi extract (1.5 mL/kg, oral gavage) or vehicle twice weekly for four weeks. Locomotor activity, anxiety-like behavior, and spatial recognition memory were assessed using the open-field, elevated-plus-maze, and object-location tests, respectively. Hippocampal fibrillar amyloid plaques were evaluated by Thioflavin-S staining, and microglial immunoreactivity and morphology were assessed using Iba1 immunofluorescence and morphometric analysis. Results: Chronic B. caapi administration did not consistently modify locomotor activity, anxiety-like behavior, or spatial recognition memory. In TG mice, treatment increased the number of hippocampal Thioflavin-S-positive fibrillar amyloid plaques, without corresponding changes in total Thioflavin-S-positive area or median plaque size. Microglial alterations were predominantly genotype-associated, with TG mice exhibiting changes in Iba1-labeled cell quantification and morphology, particularly in the CA1 region. B. caapi treatment did not significantly modify these genotype-associated morphological alterations. Conclusions: Chronic intermittent B. caapi exposure was associated with a selective change in fibrillar amyloid plaque number without parallel changes in plaque area, plaque size, behavioral performance, or microglial morphology. These findings expand current evidence regarding the biological effects of repeated B. caapi exposure in the context of established amyloid pathology.