Molecular aggregates with environmental responsive property are desired for their wide practical applications such as bio-probes. Here, we report a series of smart near-infrared (NIR) luminogens for hyperlipidemia (HLP) diagnosis. The aggregates of these molecules exhibit the twisted intramolecular charge transfer effect in aqueous medium, but aggregation-induced emission in high viscous medium due to the restriction of the intramolecular motion. We describe these aggregates, which can autonomously respond to different environments via switching of the aggregation state without changing their chemical structures, as "smart aggregates". Intriguingly, these luminogens demonstrate NIR-II and NIR-III luminescence with ultra-large Stokes shifts (> 950 nm). Both in vitro detection and in vivo imaging of HLP can be realized in a mouse model. Linear relationships exist between the emission intensity and multiple pathological parameters in blood samples of HLP patients. Thus, the design of smart aggregate facilitates rapid and accurate detection of HLP and provides a promising attempt in aggregate science. This article is protected by copyright. All rights reserved.This article is protected by copyright. All rights reserved.