In P. falciparum, antioxidant proteins of the glutathione and thioredoxin systems are compartmentalized. Some subcellular compartments have only a partial complement of these proteins. This lack of key antioxidant proteins in certain sub-cellular compartments might be compensated by functional complementation between these systems. By assessing the cross-talk between these systems, we show for the first time, that the glutathione system can reduce thioredoxins that are poor substrates for thioredoxin reductase (Thioredoxin-like protein 1 and Thioredoxin 2) and thioredoxins that lack access to thioredoxin reductase (Thioredoxin 2). Our data suggests that crosstalk between the glutathione and thioredoxin systems does exist; this could compensate for the absence of certain antioxidant proteins from key subcellular compartments.