Targeting the estrogen receptor α (ERα)-coactivator interaction prevalent in estrogen receptor-positive (ER+) breast cancers, we showcased that FTDR-stapled peptides, notably SRC2-LD, achieved superior internalization, including cytoplasmic and enriched nuclear uptake, compared to peptides stapled by ring-closing metathesis. The gene discussed is NCOA2; the disease is breast carcinoma.