Herein we discuss the differential interaction of three monosubstituted fullerene derivatives possessing pyridinium, aniline or phenothiazine end groups (F-Py, F-An and F-PTz, respectively) with calf thymus DNA (CT-DNA), probed via spectroscopic and imaging techniques. The pyridinium derivative, F-Py becomes molecularly dissolved in 10% DMSO-PBS and interacts with CT-DNA via groove binding and electrostatic interactions, leading to the initial condensation of CT-DNA into micrometer sized aggregates and subsequent precipitation. On the other hand, the aniline derivative F-An, which is reported to form nanoclusters of 3-5 nm size, interacts with DNA through ordered, chiral assemblies on the CT-DNA template, thus perturbing the highly networked structure of CT-DNA to form nanonetworks, which eventually transform into condensed aggregates. The binding interactions between CT-DNA and F-An nanoclusters were established via UV-Vis, AFM and TEM analysis, and the chiral nature of the fullerene nanocluster assemblies on CT-DNA was confirmed by the presence of induced circular dichroism that was exhibited around the 250-370 nm region, corresponding to F-An nanocluster absorption. In contrast, the phenothiazine derivative F-PTz, which forms larger nanoclusters of ∼70 nm size in 10% DMSO-PBS, exhibited only weak interactions with CT-DNA without affecting its network structure. These results demonstrate the role of the hydrophobic-hydrophilic balance in the design of DNA interacting fullerene derivatives by controlling their cluster size and interactions with CT-DNA, and are significant in applications such as DNA condensation, gene delivery and dimension controlled nanomaterial fabrication.