Objective To observe the effects of probiotics on the perioperative neurocognitive disorders (PND) of elderly rats with cardiopulmonary bypass (CPB). Methods A total of 48 adult male SD rats (SPF grade), weighing 400‒450 g were used. According to the random number table method, they were divided into four groups (n=12): a sham operation (group S), a probiotics+sham operation (group P), a CPB surgery (group C), and a probiotics+CPB (group H). Furthermore, each group was divided into two subgroups (n=6): a 7‑day group and a 28‑day group. The water maze test was performed for each group 7 days and 28 days after surgery. The rats were sacrificed under anesthesia and the right hippocampus was collected. The histological changes of hippocampal tissues were observed by hematoxylin‑eosin (H‑E) staining. The changes of PND‑associated proteins amyloid β (Aβ) protein and Tau protein in brain tissues were detected by Western blot. Results Compared with group S (compared with the subgroup at the same time, the same below), group P presented remarkably shortened average latency, extended total distance, and increases in the number of platform crossing and the amount of time spent in each quadrant 7 days and 28 days after surgery (P<0.05); groups C and H presented remarkably extended average latency, reduced total distance, and decreases in the number of platform crossing and the amount of time spent in each quadrant 7 days and 28 days after surgery (P<0.05). Compared with group P, groups C and H showed extended average latency, reduced total distance, and decreases in the number of platform crossing and the amount of time spent in each quadrant 7 days and 28 days after surgery (P<0.05). Compared with group C, group H showed shortened average latency, extended total distance, and increases in the number of platform crossing and the amount of time spent in each quadrant 7 days and 28 days after surgery (P<0.05). According to H‑E staining, there was no obvious neuronal damage in the hippocampal CA1 region of rats in group S and group P 7 days and 28 days after surgery; the degenerative changes of neurons were obvious in the hippocampal CA1 region of rats in group C 7 days and 28 days after surgery; and the damage in the hippocampal CA1 region of rats in group H was relieved compared with that in group C 7 days and 28 days after surgery. Moreover, compared with the group S, the expression of Aβ and Tau proteins significantly decreased in group P 7 days and 28 days after surgery (P<0.05), while the expression of Aβ and Tau proteins significantly increased in group H and group C 7 days and 28 days after surgery (P<0.05). Compared with group C, the expression of Aβ and Tau proteins significantly decreased in group H 7 days and 28 days after surgery (P<0.05). Conclusions Probiotics can decrease the expression of Aβ and Tau proteins, so as to improve the PND of elderly rats with CPB.