In this review, we searched PubMed, Web of Science, clinicalTrials.gov, and China Knowledge Infrastructure (CNKI) for literature and clinical trial studies, and summarized natural products based on the PI3K–AKT pathway in breast cancer treatment, involving flavonoids, polyphenols, alkaloids, and PI3K inhibitors and AKT inhibitors in clinical trials. This evidence concerns the gene PIK3CA and breast cancer.