Electrospraying of poly(butylene succinate) and its mixture with different indole derivatives was successfully performed using chloroform as solvent and relatively low flow rates and concentrations. Morphology of particles (size, diameter distribution and surface texture) and encapsulation efficiency were dependent on the loaded drug and specifically on the type of substituent (methyl or phenyl) and its position in the indole core. In general, particles showed a raisin-like morphology caused by the shell collapsing of the resulting structurally weak microspheres. Accumulation of electrosprayed particles gave rise to consistent mats and they had a more hydrophobic surface than that determined for smooth films. The increase of hydrophobicity was mainly dependent on the porosity and the hydrophobic nature of the incorporated drugs. Indole derivatives were hardly delivered in a standard phosphate saline buffer due to their scarce solubility in aqueous media but the addition of ethanol caused a drastic change in the release behavior. This was generally characterized by a fast burst effect and followed by the establishment of an equilibrium condition that was dependent on the indole derivative. However, a clearly different behavior was found when the indole was unable to form hydrogen bonds (e.g. 1-methylindole) since in this case a slow and sustained release was characteristic. Microspheres loaded with indole derivatives showed a high antiproliferative activity that was dependent on encapsulation efficiency and the type of loaded drug. The best results were specifically attained for the indole with an aromatic substituent. Interestingly significant differences were found between cancer and immortalized cells, a feature that points out the potential use of such systems for cancer prevention and treatment.