A series of four self-assembled Pt(II) molecular squares with 4,4′-dipyridyl or pyrazine bridges, including the previously reported Pt(II) squares [Pt(en)(4,4′-dipyridyl)]₄(NO₃)₈ (1), were investigated for their abilities to act as selective and effective human telomeric (htelo) G-quadruplex binders. FRET and SPR studies demonstrated that Pt(II) squares could discriminate against duplex DNA, and show promising selectivity between intramolecular G-quadruplexes. PCR-stop assays and CD studies showed that Pt(II) squares strongly induced the formation of parallel G-quadruplexes. ITC experiments indicated that Pt(II) squares could bind to the G-quadruplex with high binding constants (K_b values ranging from 10⁴–10⁸ M⁻¹). All four Pt(II) squares were effective inhibitors of human telomerase, and showed anticancer efficacy. This was particularly the case for [Pt(NH₃)₂(4,4′-dipyridyl)]₄(NO₃)₈ (2), which exhibited a 15-fold higher antiproliferative effect on A549/cisR cells than cisplatin.