Antony recommended the Central Bureau of Investigation, the country's top police authority, look into allegations several senior military officers including a former chief controller gave jobs to family members.
For the past year, the Defense Ministry's own vigilance wing has been investigating the alleged wrongdoings, the Indian Express newspaper reported.
The DRDO recently suspended a senior scientist pending an inquiry into allegations that he recruited his own daughter to a scientific post within the organization, circumventing recruitment procedures, the Express reported.
Antony's call is the latest blow to the DRDO. The agency came under heavy criticism by the Comptroller General of Defense Audit in September 2012 related to failed projects, poor spending transparency and suspected nepotism, especially at higher levels.
The Indian Express reported that the CGDA report raised serious questions about the capability of the agency that has an annual budget around $1.67 billion.
The DRDO, set up in 1958, employs 5,000 scientists with about 25,000 support staff in its 52 laboratories.
But despite the DRDO's resources of money and manpower, only 29 percent of the products developed during the past 17 years are being used by the armed forces, the Express reported.
In several cases, the DRDO bought equipment from private sector defense companies after spending millions of dollars on its own research on similar equipment.
The CGDA found after spending two years and nearly $4.8 million to develop satellite signal monitoring, the procurement agency bought very similar equipment from a public sector manufacturer for $3.9 million in April 2011.
The CGDA report said a major failure of the DRDO is that is has "no comprehensive database to find out the details of projects sanctioned for execution and how many have been declared successful."
One of the DRDO's most embarrassing projects is the 30-year development of the indigenous Tejas light combat aircraft.
Earlier this month, Antony reiterated his call for DRDO to delay no further the introduction of the Tejas, designed to replace the air force's aging MiG-21s, the Times of India reported.
Antony, addressing the Parliamentary Consultative Committee on Defense, said he wants to see the fighter's initial operational clearance planned for next month and the final operational clearance in December 2014 to be done on schedule.
He said the DRDO has as many as 532 projects under way, but he wants the agency to "concentrate on high-end research, particularly in critical and strategic areas."
The single-engine, single-pilot Tejas, being manufactured by Hindustan Aeronautics Ltd., was given the green light by the government in 1983 but it wasn't until 1988 that more concrete designs were on the drawing board.
Delays ensued, including issues over the design and performance of the intended Kaveri engine, a DRDO partnership deal with Snecma of France.
A Tejas prototype eventually flew for the first time in January 2001 -- but with a U.S.-made General Electric F-404 engine as a stop-gap.
A long-term deal with GE for 99 engines -- likely the upgraded 414 -- worth $800 million was signed this year because of further delays in the development of the Kaveri engine. GE won over Eurojet's EJ-200 engine, a report by the Deccan Herald newspaper said.
In February, AIN Online news reported the DRDO confirmed it had abandoned plans to jointly develop and produce the Kaveri military aircraft engine solely with Snecma.