Two studies were conducted to test the efficacy of guanidinoacetic acid (GAA) to spare Arg and serve as a precursor of creatine (Cr) by evaluating growth performance and muscle cellular energy homeostasis in broiler chicks. In both studies, 12 replicate pens of 6 chicks received dietary treatments beginning at day 2 post-hatch. At conclusion of each study, muscle biopsy samples were collected within 60 s of euthanasia for analysis of Cr-related energy metabolites. In study 1, Arg-deficient starter and grower basal diets were supplemented with 0 (negative control, NC), 0.06, 0.12, or 0.18% GAA, or supplemental Arg (positive control, PC; 0.37 and 0.32% L-Arg in starter and grower phases, respectively). Dietary GAA elicited graded improvements, with final BW, overall BW gain, and overall G:F being increased (
P
< 0.05) by 0.12% GAA compared with the NC diet with no difference to PC diet. Increases (
P
< 0.001) of phosphocreatine (PCr), total Cr (tCr), and glycogen concentrations, as well as the PCr-to-adenosine triphosphate (ATP) and glycogen:ATP ratios, were observed with supplementation of 0.12% GAA compared with the NC diet, even exceeding responses to the PC diet. In study 2, Arg-adequate starter and grower basal diets were supplemented with 0 (negative control, NC), 0.06, or 0.12% GAA, 0.12% Cr monohydrate (PC1), or salmon protein (PC2; containing total Arg concentrations equal to those of the NC diet in each phase and containing similar Cr as in PC1). Overall G:F was increased (
P
< 0.05) by PC1, but not by PC2, compared with the NC, while GAA supplementation elicited a response intermediate to NC and PC1 diets. However, GAA supplementation increased (
P
< 0.01) concentrations of tCr and glycogen, as well as the PCr:ATP and glycogen:ATP ratios, when compared with the NC (Arg-adequate) diet. Collectively, these data indicate that GAA can be used to replace Arg in practical, Arg-deficient diets and improve muscle energy homeostasis in broiler chicks receiving either Arg-deficient or Arg-adequate practical diets.