Chemical study of the CH2Cl2-MeOH (1:1) extract of the sponge Fascaplysinopsis reticulata collected inMayotte highlighted three new tryptophan derived alkaloids, 6,60-bis-(debromo)-gelliusine F (1), 6-bromo-8,10-dihydro-isoplysin A (2) and 5,6-dibromo-8,10-dihydro-isoplysin A (3), along with the synthetically known 8-oxo-tryptamine (4) and the three known molecules from the same family, tryptamine (5), (E)-6-bromo-20-demethyl-30-N-methylaplysinopsin (6) and (Z)-6-bromo-20-demethyl-30-N-methylaplysinopsin (7). Their structures were elucidated by 1D and 2D NMR spectra and HRESIMS data. All compounds were evaluated for their antimicrobial and their antiplasmodial activities. Regarding antimicrobial activities, the best compounds are (2) and (3), with minimum inhibitory concentration (MIC) of 0.01 and 1 µg/mL, respectively, towards Vibrionatrigens, and (5), with MIC values of 1 g/mL towards Vibrio carchariae. In addition the known 8-oxo-tryptamine (4) and the mixture of the (E)-6-bromo-20-demethyl-30-N-methylaplysinopsin (6) and (Z)-6-bromo-20-demethyl-30-N-methylaplysinopsin (7) showed moderate antiplasmodial activity against Plasmodium falciparum with IC50 values of 8.8 and 8.0 µg/mL, respectively.