A series of novel 3-(1H-indol-3-yl)pyrrolidine-2,5-dione derivatives were synthesised and evaluated for their 5-HT<sub>1A</sub>/D<sub>2</sub>/5-HT<sub>2A</sub>/5-HT<sub>6</sub>/5-HT<sub>7</sub> receptor affinity and serotonin reuptake inhibition. Most of the evaluated compounds displayed high affinities for 5-HT<sub>1A</sub> receptors (e.g., 4cK<sub>i</sub> = 2.3 nM, 4lK<sub>i</sub> = 3.2 nM). The antidepressant activity of the selected compounds was screened in vivo using the forced swim test (FST). The results indicate that compound MW005 (agonist of the pre- and postsynaptic 5-HT<sub>1A</sub> receptor) exhibited promising affinities for the 5-HT<sub>1A</sub>/SERT/D<sub>2</sub>/5-HT<sub>6</sub>/5-HT<sub>7</sub> receptors and showed an antidepressant-like activity in the FST model.