This study aimed to examine physical activity (PA) levels and mental health status (i.e., anxiety and depression) among parents of children with autism spectrum disorder (ASD). Secondary data analysis was conducted using the 2018 National Health Interview Survey. We identified 139 parents of children with ASD and 4,470 parents of children with no disability. Their PA levels, anxiety, and depression were analyzed. Compared with parents of children with no disability, parents of children with ASD were significantly less likely to meet the PA guideline for Americans and had lower odds of vigorous PA (aOR = 0.702), strengthening PA (aOR = 0.885), and light to moderate PA (aOR = 0.994). Parents of children with ASD reported significantly higher odds of anxiety (aOR = 1.559) and depression (aOR = 1.885). This study revealed lower PA levels and higher risks of anxiety and depression in parents of children with ASD.