Shrub encroachment is a serious problem in arid environments worldwide because of potential reductions in ecosystem services and negative effects on biodiversity. In southwestern USA, Chihuahuan Desert grasslands have experienced long-term encroachment by shrubs including creosotebush (Larrea tridentata). Land managers have attempted an ambitious intervention to control shrubs by spraying herbicides over extensive areas to provide grassland habitat for wildlife species of conservation concern. To provide a broader assessment of how these restoration practices affect biodiversity, we evaluated responses by four mound-building ant species (Pogonomyrmex rugosus, Aphaenogaster cockerelli, Myrmecocystus depilis, and Myrmecocystus mexicanus). We compared colony densities between 14 pairs of treated areas (herbicide applied 10–30 years before sampling) and untreated areas (spatially matched and dominated by creosotebush). P. rugosus and A. cockerelli responded positively to restoration treatments likely due to an increased abundance of seeds associated with increased grass cover. Variation in P. rugosus densities among different-aged treatments suggests a substantial time lag in response that could reflect temporal changes in habitat quality or facilitation by a keystone rodent, Dipodomys spectabilis. Colony densities of the scavenging ant M. mexicanus were reduced on treated areas, and M. depilis exhibited a similar trend, likely reflecting a reduction of liquid food resources associated with shrubs. Our results demonstrate that ongoing efforts to restore Chihuahuan Desert grasslands are having both positive and negative effects on non-target taxa such as ants and support the need for a landscape mosaic approach to restoration.