The anti‐plasmodial activity of conformationally restricted analogs of angiotensin II againstPlasmodium gallinaceumhas been described. To observe activity against anotherPlasmodiumspecies, invasion of red blood cells byPlasmodium falciparumwas analyzed. Analogs restricted with lactam or disulfide bridges were synthesized to determine their effects and constraints in the peptide–parasite interaction. The analogs were synthesized usingtert‐butoxycarbonyl and fluoromethoxycarbonyl solid phase methods, purified by liquid chromatography, and characterized by mass spectrometry.Results indicated that the lactam bridge restricted analogs 1 (Glu‐Asp‐Arg‐Orn‐Val‐Tyr‐Ile‐His‐Pro‐Phe) and 3 (Asp‐Glu‐Arg‐Val‐Orn‐Tyr‐Ile‐His‐Pro‐Phe) showed activity toward inhibition of ring formation stage ofP. falciparumerythrocytic cycle, preventing invasion in about 40% of the erythrocytes. The disulfide‐bridged analog 10 (Cys‐Asp‐Arg‐Cys‐Val‐Tyr‐Ile‐His‐Pro‐Phe) was less effective yet significant, showing a 25% decrease in infection of new erythrocytes. In all cases, the peptides presented no pressor activity, and hydrophobic interactions between the aromatic and alkyl amino acid side chains were preserved, a factor proven important in efficacy againstP. gallinaceum. In contrast, hydrophilic interactions between the Asp1carboxyl and Arg2guanidyl groups proved not to be as important as they were in the case ofP. gallinaceum,while interactions between the Arg2guanidyl and Tyr4hydroxyl groups were not important in either case. The β‐turn conformation was predominant in all of the active peptides, proving importance in anti‐plasmodial activity. This approach provides insight for understanding the importance of each amino acid residue on the native angiotensin II structure and a new direction for the design of potential chemotherapeutic agents.