This study attempts to evaluate the antimicrobial activity and the ecotoxicity of quantum dots (QDs) alone and coated with indolicidin. To meet this objective, we tested the level of antimicrobial activity on Gram-positive and Gram-negative bacteria, and we designed an ecotoxicological battery of test systems and indicators able to detect different effects using a variety of end points. The antibacterial activity was analyzed against
Staphylococcus aureus
(ATCC 6538),
Pseudomonas aeruginosa
(ATCC 1025),
Escherichia coli
(ATCC 11229), and
Klebsiella pneumoniae
(ATCC 10031), and the results showed an improved germicidal action of QDs-Ind. Toxicity studies on
Daphnia magna
indicated a decrease in toxicity for QDs-Ind compared to QDs alone, lack of bioluminescence inhibition on
Vibrio fisheri
, and no mutations in
Salmonella typhimurium TA 100
. The comet assay and oxidative stress experiments performed on
D. magna
showed a genotoxic and an oxidative damage with a dose–response trend. Indolicidin retained its activity when bound to QDs. We observed an enhanced activity for QDs-Ind. The presence of indolicidin on the surface of QDs was able to decrease its QDs toxicity.