In the search of therapeutic agents for emerging drug-resistant parasites, the synthesis of newer classes of 8-quinolinamines has emerged as a successful chemotherapeutic approach. We report synthesis of 8-quinolinamines bearing 5-alkoxy, 4-methyl, and 2-tert-butyl groups in the quinoline framework and their amino acid conjugates as broad-spectrum anti-infectives. 8-Quinolinamines exhibited potent in vitro antimalarial activity [IC50 = 20-4760 ng/mL (drug-sensitive Plasmodium falciparum D6 strain) and IC50 = 22-4760 ng/mL (drug-resistant P. falciparum W2 strain)]. The most promising analogues have cured all animals at 25 mg/kg/day against drug-sensitive Plasmodium berghei and at 50 mg/kg/day against multidrug-resistant Plasmodium yoelii nigeriensis infections in Swiss mice. The in vitro antileishmanial activities (IC50 = 0.84-5.0 μg/mL and IC90 = 1.95-7.0 μg/mL) comparable to standard drug pentamidine were exhibited by several of the synthesized 8-quinolinamines. At the same time, very promising antifungal activities (Candida albicans-IC50 = 4.93-19.38 μg/mL; Candida glabrata-IC50 = 3.96-19.22 μg/mL; Candida krusei-IC50 = 2.89-18.95 μg/mL; Cryptococcus neoformans-IC50 = 0.67-18.64 μg/mL; and Aspergillus fumigatus-IC50 = 6.0-19.32 μg/mL) and antibacterial activities (Staphylococcus aureus-IC50 = 1.33-18.9 μg/mL; methicillin-resistant S. aureus-IC50 = 1.38-15.34 μg/mL; and Mycobacterium intracellulare-IC50 = 3.12-20 μg/mL) were also observed. None of the 8-quinolinamines exhibited cytotoxicity and therefore are a promising structural class of compounds as antiparasitic and antimicrobials.