Emergency services were called to a property in Cumberworth Road, Skelmanthorpe, shortly before 7.10pm on Sunday.
Police, firefighters and paramedics attended and found a 40-year-old woman and two boys, aged 14 and 16, who were unresponsive.
All three were taken to hospital and remain there for treatment.
Detective Inspector George Bardell, of Kirklees CID, said: “Due to information received about persons being taken ill, a full emergency services response was sent to the property yesterday evening.
“While medical tests to determine the exact cause of the illness remain ongoing, due to information received, officers believe the three persons may have unknowingly come into contact with a potential illegal substance in the household.
“Enquiries are continuing today to determine exactly what has taken place and at this time, we do not believe there is any risk to the general public.
“We are not currently looking for anyone in connection with the incident.”