Cu-TMPipPrOPP and Zn-TMPipPrOPP, two new cationic metallo derivatives of TMPipPrOPP (5,10,15,20-tetrakis{4-[3-(1-methyl-1-piperidinyl)propoxy]phenyl}porphyrin), a porphyrin with four bulky side chains, were synthesized and characterized. The interactions of the new metalloporphyrins with structurally different DNAs were then compared with those of TMPipPrOPP. The introduction of bulky side chains provides the porphyrin derivatives with excellent binding specificity for G-quadruplex DNA, which is reflected by (1) the significantly different optical responses of TMPipPrOPP toward G-quadruplexes in comparison with single-stranded and duplex DNAs and (2) the ability of the three porphyrin derivatives to effectively stabilize G-quadruplexes, with no or little effect on the stability of duplex DNA. TMPipPrOPP can achieve colorimetric and fluorescent discrimination of G-quadruplexes from single-stranded and duplex DNAs with extraordinary high specificity. Due the presence of metal ions, Cu-TMPipPrOPP and Zn-TMPipPrOPP are deprived of the ability for optical G-quadruplex recognition but show enhanced ability to stabilize G-quadruplexes. In addition, because of the presence of the four cationic side chain substituents, the three porphyrin derivatives can form chiral aggregates via electrostatic interactions along the surface of structurally diverse DNAs. The chirality of aggregates formed by TMPipPrOPP is not changed by the nature of the template DNAs, whereas aggregates formed by Cu-TMPipPrOPP and Zn-TMPipPrOPP in the presence of adenine-thymine (AT) rich duplex DNA show completely inverted chirality in comparison with those formed in the presence of other DNAs. Interestingly, the chirality of the aggregates can be reversibly switched many times by alternating the ratio of Cu-TMPipPrOPP (or Zn-TMPipPrOPP) to AT-rich duplex DNA.