According to the World Health Organization, Chagas disease (CD) is the most prevalent poverty-promoting neglected tropical disease. Alarmingly, climate change is accelerating the geographical spreading of CD causative parasite, Trypanosoma cruzi, which additionally increases infection rates. Still, CD treatment remains challenging due to a lack of safe and efficient drugs. In this work, we analyze the viability of T. cruzi Akt-like kinase (TcAkt) as drug target against CD and present primary structural and functional information about a parasitic Akt protein. Nuclear Magnetic Resonance derived information in combination with Molecular Dynamics simulations offers detailed insights into structural properties of the pleckstrin homology domain of TcAkt (TcAkt-PH) and its binding to phosphatidylinositol phosphate ligands (PIP) representing an initiating step in the activation of TcAkt. Experimental data in combination with Alpha Fold predictions of TcAkt proposes a model for the mechanism of action of TcAkt involving a PIP-induced disruption of the intramolecular interface between the kinase and the PH domain resulting in an open conformation which enables kinase activity of TcAkt. Our in-depth structural analysis of TcAkt reveals potential sites for drug development with clear differences to human Akt1, located at activity essential regions like the PIP binding site and the autoinhibitory interdomain interface.