Reduced sleep quality is pronounced among the majority of the US population and is associated with decreased quality of life. The development of solutions that can aid in improving sleep quality is therefore imperative. This study examined the impact of 3 app-based interventions on physiological regulation of sleep arousal, sleep quality, and cognitive functioning using a within-subject crossover design. Participants (n = 40) were assigned to a randomized sequence of 3 active intervention conditions each with a duration of 1 week in which participants were instructed to listen to sleep music, sleepcasts, and guided mindfulness sessions for 15–45 min and a non-intervention control condition. Heart rate variability (HRV) and actigraphic measurements were collected continuously. Only the guided mindfulness intervention improved scores on the PSQI (Pittsburg Sleep Quality Inventory) from baseline to post-intervention. The actigraphy-based results showed increased sleep efficiency in the 3 active interventions compared to the non-intervention control. The HRV results showed that the 3 active interventions increased HRV during the pre-sleep period; however, only the guided mindfulness intervention increased the HRV during the sleep period compared to the non-intervention control. The results furthermore showed that the guided mindfulness intervention resulted in an increase in attentional vigilance during a cognitive task from pre- to post-intervention. Finally, a mediation analysis showed that the guided mindfulness condition had direct and indirect effects on the SART performance (Sustained Attention to Response Task), and the effect was partially mediated by HRV. These results provide support for the guided mindfulness intervention both during pre-sleep period and sleep period, and partial support for the sleep music and sleepcasts interventions restricted to the pre-sleep period. In addition, only guided mindfulness positively influenced HRV during the sleep period and showed an impact on cognitive functioning (i.e. SART performance) post-sleep.