Malaria is a serious illness transmitted through the bite of an infected mosquito, which is caused by a type of parasite called plasmodium and can be fatal if left untreated. Thus, newer antimalarials with unique mode of actions are encouraged. Fused pyridines have been vastly reported for numerous pharmacological activities including but not limited to analgesics, antitubercular, antifungal, antibacterial and antiapoptotic agents. In a current study, a series of substituted Imidazo[1,2-a]pyridine-3-carboxamides (IMPCs) (SM-IMP-01-13) along with some hydrazides (DA-01-DA-02) were synthesized and characterized by Fourier-transform infrared spectroscopy (FTIR), 1H-/13C-NMR (proton/carbon nuclear magnetic resonance), elemental analyses and mass spectra. These synthesized analogies were subjected for in vitro biological activities such as Brine Shrimp lethality (BSL), and assay of ss-hematin formation inhibitions. The BSL assay results suggested that compounds, SM-IMP-09, SM-IMP-05 were found to be less toxic and they also had comparable toxicity as of 5-Flurouracil (control) ((e.g., at 10 mu g/ml: 20% deaths of nauplii). Derivatives SM-IMP-02, and DA-05 inhibited ss-hematin formation: IC50: 1.849 and 0.042 mu M, respectively). Our molecular docking analysis on plasmodial cysteine protease falcipain-2 indicated that compound DA-05 (-9.993 kcal/mol) had highest docking score and it was comparable to standard Chloroquine (-7.673 kcal/mol). The most active molecule, DA-05 was also retained with lower HOMO-LUMO energy gap as 3.36 eV. Further, we have also analyzed MEP, and other global reactivity indexes for all IMPCs using DFT. Finally, our in-silico pharmacokinetic analysis suggested that all compounds were having good% human oral absorption values (approximate to 100%), good Caco-2 cell permeabilities (>1600 nm/s), and non-carcinogenic profiles.